Mao-b inhibitors useful for treating obesity

ABSTRACT

The invention provides novel compounds of formulae I and II:  
                 
that are monoamine oxidase-B inhibitors, which can be useful in treating obesity, diabetes, and/or cardiometabolic disorders (e.g., hypertension, dyslipidemias, high blood pressure, and insulin resistance).

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the priority benefit of U.S. Provisional Application No. 60/696,067 filed Jul. 1, 2005, now pending, which is incorporated herein by reference.

FIELD OF THE INVENTION

The present invention provides compounds and pharmaceutical compositions thereof and methods of using the same for treating obesity, diabetes, and/or cardiometabolic disorders (e.g., hypertension, dyslipidemias, high blood pressure, and insulin resistance).

BACKGROUND OF THE INVENTION

L-Selegiline is a monoamine oxidase (MAO) inhibitor that was developed for the treatment of neurological disorders and is primarily used to treat Parkinson's disease. MAO is an enzyme responsible for metabolizing biogenic monoamines including serotonin, dopamine, histamine, and phenylethylamine. By inhibiting MAO located in the central nervous system (CNS), MAO inhibitors and their analogues increase the concentration of monoamines present within the brain synapses. This enhances monoamine-mediated neurotransmission, effectively treating neurological disorders such as Parkinson's disease and depression.

MAO enzymes are also located in a number of peripheral (non-CNS) tissues, including adipose tissue, muscle, and liver. The function of MAO enzymes in these tissues has not been established. Currently, the only approved clinical use of L-selegiline and other MAO inhibitors is for the treatment of neurological disorders such as Parkinson's disease and depression.

Obesity is associated with an increase in the overall amount of adipose tissue (i.e., body fat), especially adipose tissue localized in the abdominal area. Obesity has reached epidemic proportions in the United States. The prevalence of obesity has steadily increased over the years among all racial and ethnic groups. According to the United States Surgeon General, 61% of the adult population and 14% of children are obese or overweight. Forty four million Americans are obese, with an additional eighty million deemed medically overweight. Obesity is responsible for more than 300,000 deaths annually, and will soon overtake tobacco usage as the primary cause of preventable death in the United States. Obesity is a chronic disease that contributes directly to numerous dangerous co-morbidities, including type 2 diabetes, cardiovascular disease, inflammatory diseases, premature aging, and some forms of cancer. Type 2 diabetes, a serious and life-threatening disorder with growing prevalence in both adult and childhood populations, is currently the 7^(th) leading cause of death in the United States. Since more than 80% of patients with type 2 diabetes are overweight, obesity is the greatest risk factor for developing type 2 diabetes. Increasing clinical evidence indicates that the best way to control type 2 diabetes is to reduce weight.

The most popular over-the counter drugs for the treatment of obesity, phenylpropanolamine and ephedrine, and the most popular prescription drug, fenfluramine, were removed from the marketplace as a result of safety concerns. Drugs currently approved for the long-term treatment of obesity fall into two categories: (a) CNS appetite suppressants such as sibutramine and (b) gut lipase inhibitors such as orlistat. CNS appetite suppressants reduce eating behavior through activation of the ‘satiety center’ in the brain and/or by inhibition of the ‘hunger center’ in the brain. Gut lipase inhibitors reduce the absorption of dietary fat from the gastrointestinal (GI) tract. Although sibutramine and orlistat work through very different mechanisms, they share in common the same overall goal of reducing body weight secondary to reducing the amount of calories that reach the systemic circulation. Unfortunately, these indirect therapies produce only a modest initial weight loss (approximately 5% compared to placebo) that is usually not maintained. After one or two years of treatment, most patients return to or exceed their starting weight. In addition, most approved anti-obesity therapeutics produce undesirable and often dangerous side effects that can complicate treatment and interfere with a patient's quality of life.

The lack of therapeutic effectiveness, coupled with the spiraling obesity epidemic, positions the ‘treatment of obesity’ as one of the largest and most urgent unmet medical needs. There is, therefore, a real and continuing need for the development of improved medications that treat obesity.

MAO-B inhibitors such as selegiline have been clinically useful in the treatment of CNS disorders. They have now unexpectedly been discovered to also have anti-obesity activity. Even more surprising is that the anti-obesity activity effects of MAO-B inhibitors are mediated via a peripheral (i.e., non-CNS) mechanism. This new discovery provides a novel approach for the treatment of obesity. Moreover, if the CNS effects of these compounds can be reduced, their peripherally mediated anti-obesity properties should provide therapeutic agents with greater safety. It has, as a result, become highly desirable to find MAO-B inhibitors with limited or no CNS effects. Compounds of this sort are expected to be useful in treating obesity and the variety of co-morbidities to which it contributes.

SUMMARY OF THE INVENTION

Accordingly, in an aspect, the present invention provides novel MAO-B inhibitors or stereoisomers or pharmaceutically acceptable salts that are useful to treat obesity, diabetes, and/or cardiometabolic disorders (e.g., hypertension, dyslipidemias, high blood pressure, and insulin resistance).

In another aspect, the present invention provides novel pharmaceutical compositions, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of at least one of the compounds of the present invention or a stereoisomer or pharmaceutically acceptable salt thereof.

In another aspect, the present invention provides novel methods for treating obesity, diabetes, and/or cardiometabolic disorders (e.g., hypertension, dyslipidemias, high blood pressure, and insulin resistance), comprising: administering to a patient in need thereof a therapeutically effective amount of at least one of the compounds of the present invention or a stereoisomer or pharmaceutically acceptable salt thereof.

In another aspect, the present invention provides novel methods for treating CNS disorders, comprising: administering to a patient in need thereof a therapeutically effective amount of at least one of the compounds of the present invention or a stereoisomer or pharmaceutically acceptable salt thereof.

In another aspect, the present invention provides processes for preparing novel compounds.

In another aspect, the present invention provides novel compounds or stereoisomers or pharmaceutically acceptable salts for use in therapy.

In another aspect, the present invention provides the use of novel compounds for the manufacture of a medicament for the treatment of obesity, diabetes, and/or cardiometabolic disorders.

In another aspect, the present invention provides the use of novel compounds for the manufacture of a medicament for the treatment of CNS disorders.

These and other objects, which will become apparent during the following detailed description, have been achieved by the inventors' discovery that the presently claimed compounds or stereoisomers or pharmaceutically acceptable salts thereof are expected to be effective MAO-B inhibitors.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is based on the unexpected finding that an MAO-B inhibitor is capable of reducing the amount of adipose tissue (i.e., body fat) in a warm-blooded mammal. This finding was unexpected because body fat can be reduced despite little, if any, concomitant reduction in food intake.

[1] In an embodiment, the present invention provides novel compound A or a stereoisomer or pharmaceutically acceptable salt thereof:

wherein: Y is O or H₂ and R, R¹, R², X, X¹, and Z are all independently selected from H, C₁₋₆ alkyl, and a group capable of reducing or limiting the CNS activity of compound A; and,

provided that at least one of R, R¹, R², X, X¹, and Z is other than H.

[2] In another embodiment, the present invention provides a novel compound of formula I or TI, or a stereoisomer or a pharmaceutically acceptable salt thereof:

wherein:

R, at each occurrence, is independently selected from H, C₁₋₆ alkyl, C₂₋₆ alkenyl, and C₂₋₆ alkynyl;

R¹ is selected from H, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, (CH₂)_(m)CO₂R, C₂₋₆ alkenyl-CO₂R, CH₂CH(NHAc)CO₂R, CH₂CH(NHR)CO₂R, and, (CH₂)_(n)PO(OR)₂;

R² is selected from H, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, (CH₂)_(m)CO₂R, C₂₋₆ alkenyl-CO₂R, (CH₂)_(n)CON(R)₂, (CH₂)_(n)PO(OR)₂, and (CH₂)_(n)-tetrazole;

X and X¹ are independently selected from H, OR, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, CF₃, nitro, N(R)₂, (CH₂)_(m)-tetrazole, (CH₂)_(m)CO₂R, (CH₂)_(m)CONR₂, (CH₂)_(m)CN, O(CH₂)_(n)CN, O(CH₂)_(n)-tetrazole, O(CH₂)_(n)CO₂R, O(CH₂)_(n)CON(R)₂, O—C₂₋₆ alkenyl-CO₂R, O(CH₂)_(n)PO(OR)₂, NR—C₂₋₄ alkenyl, NRSO₂CH₃, NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)CON(R)₂, NR—C₂₋₄ alkenyl-CO₂R, NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)SO₂OR, NR(CH₂)_(n)-tetrazole, NRCO(CH₂)_(n)CO₂R, NRCO(CH₂)_(n)CON(R)₂, SO₂NRCH₃, OCH₂CHMCONRCH₂CO₂R, CH₂-aryl, O(CH₂)_(n)PO(OR)₂, O(CH₂)_(n)SO₂OR, (CH₂)_(n)N⁺(R)₃A⁻, OCH₂(CH₂)_(n)N⁺(R)₃A⁻, O(CH₂)_(n)-biphenyl, O(CH₂)_(n)-biphenyl-(CH₂)_(m)CO₂R, O(CH₂)_(n)-biphenyl-(CH₂)_(m)tetrazole, O(CH₂)_(n)-biphenyl-(CH₂)_(m)CN, O(CH₂)_(n)-biphenyl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-biphenyl, NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CO₂R, NR(CH₂)_(n)-biphenyl-(CH₂)_(m)tetrazole, NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CN, NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl, O(CH₂)_(n)-heteroaryl, NR(CH₂)_(n)-aryl, NR(CH₂)_(n)-heteroaryl, O(CH₂)_(n)-aryl(CH₂)_(m)CO₂R, O(CH₂)_(n)-aryl-C₂₋₆ alkenyl-CO₂R, O(CH₂)_(n)-aryl(CH₂)_(m)-tetrazole, O(CH₂)_(n)-aryl(CH₂)_(m)CN, O(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl(CH₂)_(m)—PO(OR)₂, O(CH₂)_(n)-aryl-O(CH₂)_(n)CO₂R, O(CH₂)_(n)-aryl-O—C₂₋₆ alkenyl-CO₂R, O(CH₂)_(n)-arylO(CH₂)_(n)-tetrazole, O(CH₂)_(n)-arylO(CH₂)_(n)CN, O(CH₂)_(n)-arylO(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-arylO(CH₂), —PO(OR)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CO₂R, O(CH₂)_(n)-aryl-NRC₂₋₆ alkenyl-CO₂R, O(CH₂)_(n)-aryl-NR(CH₂)_(n)-tetrazole, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CN, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)—PO(OR)₂, NR(CH₂)_(n)-aryl(CH₂)_(m)CO₂R, NR(CH₂)_(n)-aryl-C₂₋₆ alkenyl-CO₂R, NR(CH₂)_(n)-aryl(CH₂)_(m)-tetrazole, NR(CH₂)_(n)-aryl(CH₂)_(m)CN, NR(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-aryl(CH₂)_(m)—PO(OR)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)-aryl-NR—C₂₋₆ alkenyl-CO₂R, NR(CH₂)_(n)-aryl-NR(CH₂)_(n-)tetrazole, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CN, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)-arylO(CH₂)_(n)CO₂R, NR(CH₂)_(n)-aryl-O—C₂₋₆ alkenyl-CO₂R, NR(CH₂)_(n)-aryl-O(CH₂)_(n)-tetrazole, NR(CH₂)_(n)-arylO(CH₂)_(n)CN, NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-arylO(CH₂)_(n)PO(OR)₂, O(CH₂)_(n)-heteroaryl(CH₂)_(m)CO₂R, O(CH₂)_(n)-heteroaryl-C₂₋₆ alkenyl-CO₂R, O(CH₂)_(n)-heteroaryl(CH₂)_(m)-tetrazole, O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CN, O(CH₂)_(n)-heteroaryl(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-heteroaryl(CH₂)_(m)—PO(OR)₂, O(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CO₂R, O(CH₂)_(n)-heteroaryl-O—C₂₋₆ alkenyl-CO₂R, O(CH₂)_(n)-heteroarylO(CH₂)_(n)-tetrazole, O(CH₂)_(n)-heteroaryl O(CH₂)_(n)CN, O(CH₂)_(n)-heteroarylO(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroarylO(CH₂)_(n)—PO(OR)₂, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CO₂R, O(CH₂)_(n)-heteroaryl-NR—C₂₋₆ alkenyl-CO₂R, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)-tetrazole, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CN, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-NR(CH₂), —PO(OR)₂, NR(CH₂)_(n)-heteroaryl(CH₂)_(m)CO₂R, NR(CH₂)_(n)-heteroaryl-C₂₋₆ alkenyl-CO₂R, NR(CH₂)_(n)-heteroaryl(CH₂)_(m)-tetrazole, NR(CH₂)_(n)-heteroaryl(CH₂)_(m)CN, NR(CH₂)_(n)-heteroaryl(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-heteroaryl(CH₂)_(m)—PO(OR)₂, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)-heteroaryl-NR—C₂₋₆ alkenyl-CO₂R, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)-tetrazole, NR(CH₂)_(n) heteroaryl-NR(CH₂)_(n)CN, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CO₂R, NR(CH₂)_(n)-heteroaryl-O—C₂₋₆ alkenyl-CO₂R, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n-)tetrazole, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CN, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroarylO(CH₂)_(n)PO(OR)₂, and O(CH₂CH₂O)_(p)CH₂CH₂OR³, where heteroaryl is a 5-12 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X² and tetrazole is substituted with 0-1 R;

R³ is selected from H, C₁₋₆ alkyl, and aryl-C₁₋₆ alkyl-;

X², at each occurrence, is independently selected from H, OR, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, —CN, C(O)NR₂, NRSO₂CH₃, and SO₂N(R)C₁₋₄alkyl;

A⁻, at each occurrence, is a counterion;

Y is selected from O and H₂;

Z is selected from H, OR, O(CH₂)_(n)CO₂R, O(CH₂)_(n)CONH₂, OCH₂CHMCONRCH₂CO₂R, OCH₂CH(NHC(O)CH₃)CO₂R, OCH₂CH(NHR)CO₂R, O(CH₂)_(n)PO(OR)₂, O(CH₂)_(n)SO₂OR, O(CH₂)_(n)-tetrazole, O—C₂₋₆ alkenyl, O(CH₂)_(n)-aryl, OCH₂CH₂CONRCH(OR)CO₂R, OCH₂CH₂CONRC(R)₂CH₂SO₂OR, NRR, NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)CONH₂, NRCH₂CHMCONRCH₂CO₂R, NRSO₂R, NRCH₂CH(NHC(O)CH₃)CO₂R, NRCH₂CH(NHR)CO₂R, NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)SO₂OR, NR(CH₂)_(n)-tetrazole, NR—C₂₋₆ alkenyl, NR(CH₂)_(n)-aryl, NRCH₂CH₂CONRCH(OR)CO₂R, NRCH₂CH₂CONRC(R)₂CH₂SO₂OR, and NRCO(CH₂)_(n)CO₂R, O(CH₂)_(n)-aryl-CO₂R, O(CH₂)_(n)-aryl-tetrazole, O(CH₂)_(n)-aryl-CON(R)₂, O(CH₂)_(n)-aryl-PO(OR)₂, NR(CH₂)_(n)-aryl-CO₂R, NR(CH₂)_(n)-aryl-tetrazole, NR(CH₂)_(n)-aryl-CON(R)₂, and NR(CH₂)_(n)-aryl-PO(OR)₂, wherein aryl is substituted with 1-2 X² and tetrazole is substituted with 0-1 R;

when Y is H₂, Z¹ is selected from H, OR, O(CH₂)_(n)CO₂R, O(CH₂)_(n)CONH₂, OCH₂CHMCONRCH₂CO₂R, OCH₂CH(NHC(O)CH₃)CO₂R, OCH₂CH(NHR)CO₂R, O(CH₂)_(n)PO(OR)₂, O(CH₂)_(n)SO₂OR, O—C₂₋₆ alkenyl, O(CH₂)_(n)-aryl, NR(CH₂)_(n)-aryl, OCH₂CH₂CONRCH(OR)CO₂R, OCH₂CH₂CONRC(R)₂CH₂SO₂OR, and NRCO(CH₂)_(n)CO₂R, wherein aryl is substituted with 1-2 X²;

when Y is O, Z¹ is selected from OR, NRR, NR(CH₂)_(n)CONH₂, NR—C₂₋₆ alkyl O(CH₂)_(n)-aryl, and NR(CH₂)_(n)-aryl, wherein aryl is substituted with 1-2 X²;

M is selected from H, C₁₋₆ alkyl, C₃₋₈ cycloalkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, aryl, 5-12 membered heteroaryl consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, (CH₂)_(n)-aryl, and (CH₂)_(n)-5-12 membered heteroaryl consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, wherein aryl and heteroaryl are substituted with 1-2 X²;

Q is selected from O⁻, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, (CH₂)_(n)-aryl, and (CH₂)_(n)-5-12 membered heteroaryl consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, wherein aryl and heteroaryl are substituted with 1-2 X²;

provided that when Q is other than O⁻, then A⁻ is present;

m is selected from 0, 1, 2, 3, and 4;

n is selected from 1, 2, 3, and 4;

p is selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11; and,

provided that in formula I:

(a) R is other than H and CH₃,

(b) C(═Y)Z is other than CH₃; and/or

(c) at least one of R¹, R², X, and X¹ is other than H;

further provided that at least one of X and X¹ is other than H, alkyl, alkoxy, hydroxy, and halo.

In another variant, the compounds of the present invention have no more than one acid functionality.

[3] In another embodiment, the present invention provides a novel compound of formula Ia, or a stereoisomer or a pharmaceutically acceptable salt thereof:

wherein:

R, at each occurrence, is independently selected from H and C₁₋₄ alkyl;

R¹ is selected from H and C₁₋₄ alkyl;

X and X¹ are independently selected from H, OR, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl, N(R)₂, (CH₂)_(m)CONR₂, (CH₂)_(m)CN, NRSO₂CH₃, NRCO(CH₂)_(n)CON(R)₂, SO₂NRCH₃, CH₂N(C₁₋₄ alkyl)₂, CH₂-aryl, CH₂-heteroaryl, O(CH₂)_(n)-aryl, O(CH₂)_(n)-heteroaryl, NR(CH₂)_(n)-aryl, NR(CH₂)_(n)-heteroaryl, O(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-biphenyl, O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CON(R)₂, NR(CH₂)_(n)-biphenyl, NR(CH₂)_(n)-biphenyl-CN, and NR(CH₂)_(n)-biphenyl-CONH₂, and O(CH₂CH₂O)_(p)CH₂CH₂OR³, where heteroaryl is a 5-10 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S; and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X²,

R³ is selected from H, C₁₋₄ alkyl, and aryl-C₁₋₁₄ alkyl-;

X², at each occurrence, is independently selected from H, OR, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, —CN, C(O)NR₂, NRSO₂CH₃, and SO₂N(R)C₁₋₄alkyl; and,

provided that at least one of X and X¹ is other than H, alkyl, alkoxy, hydroxy, and halo.

[3a] In another embodiment, the present invention provides a novel compound of formula Ia, or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein:

one of X and X¹ is H and the other selected from C₂₋₄ alkenyl, C₂₋₄ alkynyl, CF₃, nitro, O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl, N(R)₂, (CH₂)_(m)CONR₂, (CH₂)_(m)CN, NRCO(CH₂)_(n)CON(R)₂, NRSO₂CH₃, SO₂NRCH₃, CH₂N(C₁₋₄ alkyl)₂, CH₂-aryl, CH₂-heteroaryl, O(CH₂)_(n)-aryl, O(CH₂)_(n)-heteroaryl, NR(CH₂)_(n)-aryl, NR(CH₂)_(n)-heteroaryl, O(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-biphenyl, O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CON(R)₂, NR(CH₂)_(n)-biphenyl, NR(CH₂)_(n)-biphenyl-CN, and NR(CH₂)_(n)-biphenyl-CONH₂, and O(CH₂CH₂O)_(p)CH₂CH₂OR³, where heteroaryl is a 5-10 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S; and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X².

[4] In another embodiment, the present invention provides a novel compound of formula Ib, or a stereoisomer or a pharmaceutically acceptable salt thereof:

wherein:

R, at each occurrence, is independently selected from H and C₁₋₄ alkyl;

R¹ is selected from (CH₂)_(m)CO₂R, C₂₋₄ alkenyl-CO₂R, CH₂CH(NHAc)CO₂R, CH₂CH(NHR)CO₂R, and, (CH₂)_(n)PO(OR)₂;

X and X¹ are independently selected from H, OR, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl, N(R)₂, (CH₂)_(m)CONR₂, (CH₂)_(m)CN, NRCO(CH₂)CON(R)₂, NRSO₂CH₃, SO₂NRCH₃, CH₂N(C₁₋₄ alkyl)₂, CH₂-aryl, CH₂-heteroaryl, O(CH₂)_(n)-aryl, O(CH₂)_(n)-heteroaryl, NR(CH₂)_(n)-aryl, NR(CH₂)_(n)-heteroaryl, O(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-aryl-H(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-biphenyl, O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CONH₂, NR(CH₂)_(n)-biphenyl, NR(CH₂)_(n)-biphenyl-CN, NR(CH₂)_(n)biphenyl-CONH₂, and O(CH₂CH₂O)_(p)CH₂CH₂OR³, where heteroaryl is a 5-10 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X²;

R³ is selected from H, C₁₋₄ alkyl, and aryl-C₁₋₄ alkyl-;

X², at each occurrence, is independently selected from H, OR, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, —CN, C(O)NR₂, NRSO₂CH₃, and SO₂N(R)C₁₋₄alkyl;

M is selected from H, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, (CH₂)_(n)-aryl, and (CH₂)_(n)-5-10 membered heteroaryl consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, wherein aryl and heteroaryl are substituted with 1-2 X²; and,

provided that in formula Ib:

(a) R is other than H and CH₃, and/or

(b) at least one of R¹, X, and X¹ is other than H;

further provided that at least one of X and X¹ is other than H, alkyl, alkoxy, hydroxy, and halo.

[4a] In another embodiment, the present invention provides a novel compound of formula Ib, or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein:

one of X and X¹ is H and the other selected from C₂₋₄ alkenyl, C₂₋₄ alkynyl, CF₃, nitro, O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl, N(R)₂, (CH₂)_(m)CONR₂, (CH₂)_(m)CN, NRCO(CH₂)_(n)CON(R)₂, NRSO₂CH₃, SO₂NRCH₃, CH₂N(C₁₋₄ alkyl)₂, CH₂-aryl, CH₂-heteroaryl, O(CH₂)_(n)-aryl, O(CH₂)_(n)-heteroaryl, NR(CH₂)_(n)-aryl, NR(CH₂)_(n)-heteroaryl, O(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-biphenyl, O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CONH₂, NR(CH₂)_(n)-biphenyl, NR(CH₂)_(n)-biphenyl-CN, NR(CH₂)_(n)-biphenyl-CONH₂, and O(CH₂CH₂O)_(p)CH₂CH₂OR³, where heteroaryl is a 5-10 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X².

[5] In another embodiment, the present invention provides a novel compound of formula Ic, or a stereoisomer or a pharmaceutically acceptable salt thereof:

wherein:

R, at each occurrence, is independently selected from H and C₁₋₄ alkyl;

R¹ is selected from H and C₁₋₄ alkyl;

X and X¹ are independently selected from H, OR, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl, N(R)₂, (CH₂)_(m)CONR₂, (CH₂)_(m)CN, NRCO(CH₂)_(n)CON(R)₂, NRSO₂CH₃, SO₂NRCH₃, CH₂N(C₁₋₄ alkyl)₂, CH₂-aryl, CH₂-heteroaryl, O(CH₂)_(n)-aryl, O(CH₂)_(n)-heteroaryl, NR(CH₂)_(n)-aryl, NR(CH₂)_(n)-heteroaryl, O(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-biphenyl, O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CONH₂, NR(CH₂)_(n)-biphenyl, NR(CH₂)_(n)-biphenyl-CN, NR(CH₂)_(n)-biphenyl-CONH₂, and O(CH₂CH₂O)_(p)CH₂CH₂OR³, where heteroaryl is a 5-10 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X²;

R³ is selected from H, C₁₋₄ alkyl, and aryl-C₁₋₄ alkyl-;

X², at each occurrence, is independently selected from H, OR, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, —CN, C(O)NR₂, NRSO₂CH₃, and SO₂N(R)C₁₋₄alkyl;

A⁻ is selected from Cl⁻ and Br⁻;

Z is selected from O(CH₂)_(n)CO₂R, O(CH₂)_(n)CONH₂, O(CH₂)_(n)PO(OR)₂, O(CH₂)_(n)SO₂OR, O(CH₂)_(n)-tetrazole, NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)CONH₂, NRCH₂CHMCONRCH₂CO₂R, NRSO₂R, NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)SO₂OR, NR(CH₂)_(n)-tetrazole, NRCO(CH₂)_(n)CO₂R, O(CH₂)_(n)-phenyl-CO₂R, O(CH₂)_(n)-phenyl-tetrazole, O(CH₂)_(n)-phenyl-CON(R)₂, O(CH₂)_(n)-phenyl-PO₃(R)₂, NR(CH₂)_(n)-phenyl-CO₂R, NR(CH₂)_(n)-phenyl-tetrazole, NR(CH₂)_(n)-phenyl-CON(R)₂, and NR(CH₂)_(n)-phenyl-PO₃(R)₂, wherein phenyl is substituted with 1-2 X² and tetrazole is substituted with 0-1 R; and,

M is selected from H, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, (CH₂)_(n)-aryl, and (CH₂)_(n)-5-10 membered heteroaryl consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, wherein aryl and heteroaryl are substituted with 1-2 X²; and,

provided that at least one of X and X¹ is other than H, alkyl, alkoxy, hydroxy, and halo.

[5a] In another embodiment, the present invention provides a novel compound of formula Ic, or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein:

one of X and X¹ is H and the other selected from C₂₋₄ alkenyl, C₂₋₄ alkynyl, CF₃, nitro, O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl, N(R)₂, (CH₂)_(m)CONR₂, (CH₂)_(m)CN, NRCO(CH₂)_(n)CON(R)₂, NRSO₂CH₃, SO₂NRCH₃, CH₂N(C₁₋₄ alkyl)₂, CH₂-aryl, CH₂-heteroaryl, O(CH₂)_(n)-aryl, O(CH₂)_(n)-heteroaryl, NR(CH₂)_(n)-aryl, NR(CH₂)_(n)-heteroaryl, O(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-biphenyl, O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CONH₂, NR(CH₂)_(n)-biphenyl, NR(CH₂)_(n)-biphenyl-CN, NR(CH₂)_(n)-biphenyl-CONH₂, and O(CH₂CH₂O)_(p)CH₂CH₂OR³, where heteroaryl is a 5-10 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X².

[6] In another embodiment, the present invention provides a novel compound of formula Ic, or a stereoisomer or a pharmaceutically acceptable salt thereof:

wherein:

R, at each occurrence, is independently selected from H and C₁₋₄ alkyl;

R¹ is selected from H, C₁₋₄ alkyl, (CH₂)_(m)CO₂R, C₂₋₄ alkenyl-CO₂R, CH₂CH(NHAc)CO₂R, CH₂CH(NHR)CO₂R, and, (CH₂)_(n)PO(OR)₂;

X and X¹ are independently selected from H, OR, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, N(R)₂, (CH₂)_(m)-tetrazole, (CH₂)_(m)CO₂R, (CH₂)_(m)CONR₂, (CH₂)_(m)CN, O(CH₂)_(n)CN, O(CH₂)_(n)-tetrazole, O(CH₂)_(n)CO₂R, O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl-CO₂R, O(CH₂)_(n)PO(OR)₂, NR—C₂₋₄ alkenyl, NRSO₂CH₃, NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)CON(R)₂, NR—C₂₋₄ alkenyl-CO₂R, NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)SO₂OR, NR(CH₂)_(n)-tetrazole, NRCO(CH₂)_(n)CO₂R, NRCO(CH₂)_(n)CON(R)₂, SO₂NRCH₃, OCH₂CHMCONRCH₂CO₂R, CH₂-aryl, O(CH₂)_(n)PO(OR)₂, O(CH₂)_(n)SO₂R, (CH₂)_(n)N⁺(R)₃A⁻, OCH₂(CH₂)_(n)N⁺(R)₃A⁻, O(CH₂)_(n)-biphenyl, O(CH₂)_(n)-biphenyl-(CH₂)_(m)CO₂R, O(CH₂)_(n)-biphenyl-(CH₂)_(m)tetrazole, O(CH₂)_(n)-biphenyl-(CH₂)_(m)CN, O(CH₂)_(n)-biphenyl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-biphenyl, NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CO₂R, NR(CH₂)_(n)-biphenyl-(CH₂)_(m)tetrazole, NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CN, NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl, O(CH₂)_(n)-heteroaryl, NR(CH₂)_(n)-aryl, NR(CH₂)_(n)-heteroaryl, O(CH₂)_(n)-aryl(CH₂)_(m)CO₂R, O(CH₂)_(n)-aryl-C₂₋₄ alkenyl-CO₂R, O(CH₂)_(n)-aryl(CH₂)_(m)-tetrazole, O(CH₂)_(n)-aryl(CH₂)_(m)CN, O(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl(CH₂)_(m)—PO(OR)₂, O(CH₂)_(n)-aryl-O(CH₂)_(n)CO₂R, O(CH₂)_(n)-aryl-O—C₂₋₄ alkenyl-CO₂R, O(CH₂)_(n)-arylO(CH₂)_(n)-tetrazole, O(CH₂)_(n)-arylO(CH₂)_(n)CN, O(CH₂)_(n)-arylO(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-arylO(CH₂), —PO(OR)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CO₂R, O(CH₂)_(n)-aryl-NRC₂₋₄ alkenyl-CO₂R, O(CH₂)_(n)-aryl-NR(CH₂)_(n)-tetrazole, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CN, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)—PO(OR)₂, NR(CH₂)_(n)-aryl(CH₂)_(m)CO₂R, NR(CH₂)_(n)-aryl-C₂₋₄ alkenyl-CO₂R, NR(CH₂)_(n)-aryl(CH₂)_(m)-tetrazole, NR(CH₂)_(n)-aryl(CH₂)_(m)CN, NR(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-aryl(CH₂)_(m)—PO(OR)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)-aryl-NR—C₂₋₄ alkenyl-CO₂R, NR(CH₂)_(n)-aryl-NR(CH₂)_(n-)tetrazole, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CN, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)-arylO(CH₂)_(n)CO₂R, NR(CH₂)_(n)-aryl-O—C₂₋₄ alkenyl-CO₂R, NR(CH₂)_(n)-aryl-O(CH₂)_(n-)tetrazole, NR(CH₂)_(n)-arylO(CH₂)_(n)CN, NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-arylO(CH₂)_(n)PO(OR)₂, O(CH₂)_(n)-heteroaryl(CH₂)_(m)CO₂R, O(CH₂)_(n)-heteroaryl-C₂₋₄ alkenyl-CO₂R, O(CH₂)_(n)-heteroaryl(CH₂)_(m)-tetrazole, O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CN, O(CH₂)_(n)-heteroaryl(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-heteroaryl(CH₂)_(m)—PO(OR)₂, O(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CO₂R, O(CH₂)_(n)-heteroaryl-O—C₂₋₄ alkenyl-CO₂R, O(CH₂)_(n)-heteroarylO(CH₂)_(n)-tetrazole, O(CH₂)_(n)-heteroaryl O(CH₂)_(n)CN, O(CH₂)_(n)-heteroarylO(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroarylO(CH₂)_(n)—PO(OR)₂, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CO₂R, O(CH₂)_(n)-heteroaryl-NR—C₂₋₄ alkenyl-CO₂R, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)-tetrazole, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CN, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-NR(CH₂), —PO(OR)₂, NR(CH₂)_(n)-heteroaryl(CH₂)_(m)CO₂R, NR(CH₂)_(n)-heteroaryl-C₂₋₄ alkenyl-CO₂R, NR(CH₂)_(n)-heteroaryl(CH₂)_(m)-tetrazole, NR(CH₂)_(n)-heteroaryl(CH₂)_(m)CN, NR(CH₂)_(n)-heteroaryl(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-heteroaryl(CH₂)_(m)—PO(OR)₂, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)-heteroaryl-NR—C₂₋₄ alkenyl-CO₂R, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n-)tetrazole, NR(CH₂)_(n) heteroaryl-NR(CH₂)_(n)CN, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CO₂R, NR(CH₂)_(n)-heteroaryl-O—C₂₋₄ alkenyl-CO₂R, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)-tetrazole, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CN, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroarylO(CH₂)_(n)PO(OR)₂, and O(CH₂CH₂O)_(p)CH₂CH₂OR³, where heteroaryl is a 5-12 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X² and tetrazole is substituted with 0-1 R;

R³ is selected from H, C₁₋₄ alkyl, and aryl-C₁₋₄ alkyl-;

X², at each occurrence, is independently selected from H, OR, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, —CN, C(O)NR₂, NRSO₂CH₃, and SO₂N(R)C₁₋₄alkyl;

A⁻, at each occurrence, is selected from Cl⁻ and Br⁻;

Z is selected from H, OH, halogen, CF₃, C₁₋₄ alkoxy, O—C₂₋₄ alkenyl, O(CH₂)_(n)CONH₂, OCH₂-aryl, NRR, NR—C₂₋₄ alkenyl, NR(CH₂)_(n)CONH₂, NR(CH₂)_(n)-aryl, and NRCO(CH₂)_(n)CO₂R, wherein aryl is substituted with 1-2 X²;

M is selected from H, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, (CH₂)_(n)-aryl, and (CH₂)_(n)-5-10 membered heteroaryl consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S; and, wherein aryl and heteroaryl are substituted with 1-2 X²; and,

provided that in formula Ic:

(a) R is other than H and CH₃,

(b) Z is other than H; and/or

(c) at least one of R¹, X, and X¹ is other than H;

further provided that at least one of X and X¹ is other than H, alkyl, alkoxy, hydroxy, and halo.

[6a] In another embodiment, the present invention provides a novel compound of formula Ic, or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein:

one of X and X¹ is H and the other selected from C₂₋₄ alkenyl, C₂₋₄ alkynyl, CF₃, nitro, N(R)₂, (CH₂)_(m)-tetrazole, (CH₂)_(m)CO₂R, (CH₂)_(m)CONR₂, (CH₂)_(m)CN, O(CH₂)_(n)CN, O(CH₂)_(n)-tetrazole, O(CH₂)_(n)CO₂R, O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl-CO₂R, O(CH₂)_(n)PO(OR)₂, NR—C₂₋₄ alkenyl, NRSO₂CH₃, NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)CON(R)₂, NR—C₂₋₄ alkenyl-CO₂R, NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)SO₂OR, NR(CH₂)_(n)-tetrazole, NRCO(CH₂)_(n)CO₂R, NRCO(CH₂)_(n)CON(R)₂, SO₂NRCH₃, OCH₂CHMCONRCH₂CO₂R, CH₂-aryl, O(CH₂)_(n)PO(OR)₂, O(CH₂)_(n)SO₂OR, (CH₂)_(n)N⁺(CH₃)₃A⁻, OCH₂(CH₂)_(n)N⁺(CH₃)₃A⁻, O(CH₂)_(n)-biphenyl, O(CH₂)_(n)-biphenyl-(CH₂)_(m)CO₂R, O(CH₂)_(n)-biphenyl-(CH₂)_(m)tetrazole, O(CH₂)_(n)-biphenyl-(CH₂)_(m)CN, O(CH₂)_(n)-biphenyl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-biphenyl, NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CO₂R, NR(CH₂)_(n)-biphenyl-(CH₂)_(m)tetrazole, NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CN, NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl, O(CH₂)_(n)-heteroaryl, NR(CH₂)_(n)-aryl, NR(CH₂)_(n)-heteroaryl, O(CH₂)_(n)-aryl(CH₂)_(m)CO₂R, O(CH₂)_(n)-aryl-C₂₋₄ alkenyl-CO₂R, O(CH₂)_(n)-aryl(CH₂)_(m)-tetrazole, O(CH₂)_(n)-aryl(CH₂)_(m)CN, O(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl(CH₂)_(m)—PO(OR)₂, O(CH₂)_(n)-aryl-O(CH₂)_(n)CO₂R, O(CH₂)_(n)-aryl-O—C₂₋₄ alkenyl-CO₂R, O(CH₂)_(n)-arylO(CH₂)_(n)-tetrazole, O(CH₂)_(n)-arylO(CH₂)_(n)CN, O(CH₂)_(n)-arylO(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-arylO(CH₂), —PO(OR)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CO₂R, O(CH₂)_(n)-aryl-NRC₂₋₄ alkenyl-CO₂R, O(CH₂)_(n)-aryl-NR(CH₂)_(n)-tetrazole, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CN, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)—PO(OR)₂, NR(CH₂)_(n)-aryl(CH₂)_(m)CO₂R, NR(CH₂)_(n)-aryl-C₂₋₄ alkenyl-CO₂R, NR(CH₂)_(n)-aryl(CH₂)_(m)-tetrazole, NR(CH₂)_(n)-aryl(CH₂)_(m)CN, NR(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-aryl(CH₂)_(m)—PO(OR)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)-aryl-NR—C₂₋₄ alkenyl-CO₂R, NR(CH₂)_(n)-aryl-NR(CH₂)_(n-)tetrazole, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CN, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)-arylO(CH₂)_(n)CO₂R, NR(CH₂)_(n)-aryl-O—C₂₋₄ alkenyl-CO₂R, NR(CH₂)_(n)-aryl-O(CH₂)_(n-)tetrazole, NR(CH₂)_(n)-arylO(CH₂)_(n)CN, NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-arylO(CH₂)_(n)PO(OR)₂, O(CH₂)_(n)-heteroaryl(CH₂)_(m)CO₂R, O(CH₂)_(n)-heteroaryl-C₂₋₄ alkenyl-CO₂R, O(CH₂)_(n)-heteroaryl(CH₂)_(m)-tetrazole, O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CN, O(CH₂)_(n)-heteroaryl(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-heteroaryl(CH₂)_(m)—PO(OR)₂, O(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CO₂R, O(CH₂)_(n)-heteroaryl-O—C₂₋₄ alkenyl-CO₂R, O(CH₂)_(n)-heteroarylO(CH₂)_(n)-tetrazole, O(CH₂)_(n)-heteroaryl O(CH₂)_(n)CN, O(CH₂)_(n)-heteroarylO(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroarylO(CH₂)_(n)—PO(OR)₂, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CO₂R, O(CH₂)_(n)-heteroaryl-NR—C₂₋₄ alkenyl-CO₂R, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)-tetrazole, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CN, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)—PO(OR)₂, NR(CH₂)_(n)-heteroaryl(CH₂)_(m)CO₂R, NR(CH₂)_(n)-heteroaryl-C₂₋₄ alkenyl-CO₂R, NR(CH₂)_(n)-heteroaryl(CH₂)_(m)-tetrazole, NR(CH₂)_(n)-heteroaryl(CH₂)_(m)CN, NR(CH₂)_(n)-heteroaryl(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-heteroaryl(CH₂)_(m)—PO(OR)₂, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)-heteroaryl-NR—C₂₋₄ alkenyl-CO₂R, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)-tetrazole, NR(CH₂)_(n) heteroaryl-NR(CH₂)_(n)CN, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CO₂R, NR(CH₂)_(n)-heteroaryl-O—C₂₋₄ alkenyl-CO₂R, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n-)tetrazole, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CN, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroarylO(CH₂)_(n)PO(OR)₂, and O(CH₂CH₂O)_(p)CH₂CH₂OR³, where heteroaryl is a 5-12 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X² and tetrazole is substituted with 0-1 R.

[7] In another embodiment, the present invention provides a novel compound of formula Ic, or a stereoisomer or a pharmaceutically acceptable salt thereof:

wherein:

R, at each occurrence, is independently selected from H and C₁₋₄ alkyl;

R¹ is selected from H and C₁₋₄ alkyl;

X and X¹ are independently selected from H, OR, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl, N(R)₂, (CH₂)_(m)CONR₂, (CH₂)_(m)CN, NRCO(CH₂)CON(R)₂, NRSO₂CH₃, SO₂NRCH₃, CH₂N(C₁₋₄ alkyl)₂, CH₂-aryl, CH₂-heteroaryl, O(CH₂)_(n)-aryl, O(CH₂)_(n)-heteroaryl, NR(CH₂)_(n)-aryl, NR(CH₂)_(n)-heteroaryl, O(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-biphenyl, O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CONH₂, NR(CH₂)_(n)-biphenyl, NR(CH₂)_(n)-biphenyl-CN, NR(CH₂)_(n)-biphenyl-CONH₂, and O(CH₂CH₂O)_(p)CH₂CH₂OR³, where heteroaryl is a 5-10 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X²;

R³ is selected from H, C₁₋₄ alkyl, and aryl-C₁₋₄ alkyl-;

X², at each occurrence, is independently selected from H, OR, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, —CN, C(O)NR₂, NRSO₂CH₃, and SO₂N(R)C₁₋₄alkyl; and,

Z is selected from H, OH, C₁₋₄ alkoxy, O—C₂₋₄ alkenyl, O(CH₂)_(n)CONH₂, OCH₂-aryl, NRR, NR—C₂₋₄ alkenyl, NR(CH₂)_(n)CONH₂, and NRCH₂-aryl, wherein aryl is substituted with 1-2 X²; and,

provided that at least one of X and X¹ is other than H, alkyl, alkoxy, hydroxy, and halo.

[7a] In another embodiment, the present invention provides a novel compound of formula Ic, or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein:

one of X and X¹ is H and the other selected from C₂₋₄ alkenyl, C₂₋₄ alkynyl, CF₃, nitro, O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl, N(R)₂, (CH₂)_(m)CONR₂, (CH₂)_(m)CN, NRCO(CH₂)_(n)CON(R)₂, NRSO₂CH₃, SO₂NRCH₃, CH₂N(C₁₋₄ alkyl)₂, CH₂-aryl, CH₂-heteroaryl, O(CH₂)_(n)-aryl, O(CH₂)_(n)-heteroaryl, NR(CH₂)_(n)-aryl, NR(CH₂)_(n)-heteroaryl, O(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl-(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, O(CH₂)N-heteroaryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-biphenyl, O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CONH₂, NR(CH₂)_(b)-biphenyl, NR(CH₂)_(n)-biphenyl-CN, NR(CH₂)_(n)-biphenyl-CONH₂, and O(CH₂CH₂O)_(p)CH₂CH₂OR³, where heteroaryl is a 5-10 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X².

[8] In another embodiment, the present invention provides a novel compound of formula IIa, or a stereoisomer or a pharmaceutically acceptable salt thereof:

wherein:

R, at each occurrence, is independently selected from H and C₁₋₆ alkyl;

R¹ is selected from H and C₁₋₄ alkyl;

R² is selected from H and C₁₋₄ alkyl;

X and X¹ are independently selected from H, OR, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl, (CH₂)_(m)CONR₂, (CH₂)_(m)CN, NRCO(CH₂)_(n)CON(R)₂, NRSO₂CH₃, SO₂NRCH₃, CH₂-aryl, CH₂-heteroaryl, O(CH₂)_(n)-aryl, O(CH₂)_(n)-heteroaryl, NR(CH₂)_(n)-aryl, NR(CH₂)_(n)-heteroaryl, O(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-aryl; O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-biphenyl, O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CONH₂, NR(CH₂)_(n)-biphenyl, NR(CH₂)_(n)-biphenyl-CN, and NR(CH₂)_(n)-biphenyl-CONH₂, and O(CH₂CH₂O)_(p)CH₂CH₂OR³, where heteroaryl is a 5-10 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X²;

R³ is selected from H, C₁₋₄ alkyl, and aryl-C₁₋₄ alkyl-;

X², at each occurrence, is independently selected from H, OR, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, —CN, C(O)NR₂, NRSO₂CH₃, and SO₂N(R)C₁₋₄alkyl;

Y is selected from O and H₂;

when Y is H₂, Z¹ is selected from H and OR;

when Y is O, Z¹ is selected from NRR, NR(CH₂)_(n)CONH₂, NR—C₂₋₄ alkenyl, and NR(CH₂)_(n)-aryl, wherein aryl is substituted with 1-2 X²;

Q is selected from O⁻, C₁₋₄ alkyl, C₃₋₄ alkenyl, and C₃₋₄ alkynyl; and,

provided that when Q is other than O⁻, A⁻ is present and is selected from Cl and Br;

further provided that at least one of X and X¹ is other than H, alkyl, alkoxy, hydroxy, and halo.

[8a] In another embodiment, the present invention provides a novel compound of formula IIa, or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein:

one of X and X¹ is H and the other selected from C₂₋₄ alkenyl, C₂₋₄ alkynyl, CF₃, nitro, O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl, (CH₂)_(m)CONR₂, (CH₂)_(m)CN, NRCO(CH₂)_(n)CON(R)₂, NRSO₂CH₃, SO₂NRCH₃, CH₂-aryl, CH₂-heteroaryl, O(CH₂)_(n)-aryl, O(CH₂)_(n)-heteroaryl, NR(CH₂)_(n)-aryl, NR(CH₂)_(n)-heteroaryl, O(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-aryl, O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-biphenyl, O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CONH₂, NR(CH₂)_(n)-biphenyl, NR(CH₂)_(n)-biphenyl-CN, and NR(CH₂)_(n)-biphenyl-CONH₂, and O(CH₂CH₂O)_(p)CH₂CH₂OR³, where heteroaryl is a 5-10 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X².

In another embodiment, the present invention provides novel pharmaceutical compositions, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of the present invention or a stereoisomer or pharmaceutically acceptable salt thereof.

In another embodiment, the present invention provides a novel method for treating a disease, comprising: administering to a patient in need thereof a therapeutically effective amount of a compound of the present invention or a stereoisomer or pharmaceutically acceptable salt thereof, wherein the disease is selected from obesity, diabetes, cardiometabolic disorders, and a combination thereof.

In another embodiment, the cardiometabolic disorder is selected from hypertension, dyslipidemias (e.g., undesirable blood lipid levels, elevated cholesterol levels, and lowered LDL levels), high blood pressure, and insulin resistance.

In another embodiment, the present invention provides a novel method for treating a co-morbidity of obesity, comprising: administering to a patient in need thereof a therapeutically effective amount of a compound of the present invention or a stereoisomer or pharmaceutically acceptable salt thereof.

In another embodiment, the present invention provides a novel method for treating a co-morbidity of obesity, comprising: administering to a patient in need thereof a therapeutically effective amount of a compound of the present invention or a stereoisomer or pharmaceutically acceptable salt thereof.

In another embodiment, the co-morbidity is selected from diabetes, Metabolic Syndrome, dementia, and heart disease.

In another embodiment, the co-morbidity is selected from hypertension; gallbladder disease; gastrointestinal disorders; menstrual irregularities; degenerative arthritis; venous statis ulcers; pulmonary hypoventilation syndrome; sleep apnea; snoring; coronary artery disease; arterial sclerotic disease; pseudotumor cerebri; accident proneness; increased risks with surgeries; osteoarthritis; high cholesterol; and, increased incidence of malignancies of the ovaries, cervix, uterus, breasts, prostrate, and gallbladder.

In another embodiment, the present invention provides a novel method for treating a CNS disorder, comprising: administering to a patient in need thereof a therapeutically effective amount of a compound of the present invention or a stereoisomer or pharmaceutically acceptable salt thereof.

In another embodiment, the CNS disorder is selected from acute and chronic neurological disorders, cognitive disorders, and memory deficits. Examples of these disorders include chronic or traumatic degenerative processes of the nervous system, which include Alzheimer's disease, other types of dementia, minimal cognitive impairment, and Parkinson's disease. Other examples of CNS disorders include psychiatric diseases, which include depression, anxiety, panic attack, social phobia, schizophrenia, and anorexia. Further examples of CNS disorders include withdrawal syndromes induced by alcohol, nicotine and other addictive drugs. Additional examples of CNS disorders include neuropathic pain and neuroinflamatory diseases (e.g., multiple sclerosis).

In another embodiment, the present invention also provides a method of preventing or reversing the deposition of adipose tissue in a mammal by the administration of a MAO-B inhibitor. By preventing or reversing the deposition of adipose tissue, MAO-B inhibitors are expected to reduce the incidence or severity of obesity, thereby reducing the incidence or severity of associated co-morbidities.

In another embodiment, the present invention provides a compound of the present invention for use in therapy.

In another embodiment, the present invention provides the use of compounds of the present invention for the manufacture of a medicament for the treatment of obesity, diabetes, cardiometabolic disorders, and a combination thereof.

In another embodiment, the present invention provides the use of novel compounds for the manufacture of a medicament for the treatment of CNS disorders.

The present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof. This invention encompasses all combinations of preferred aspects of the invention noted herein. It is understood that any and all embodiments of the present invention may be taken in conjunction with any other embodiment or embodiments to describe additional more preferred embodiments. It is also to be understood that each individual element of the preferred embodiments is intended to be taken individually as its own independent preferred embodiment. Furthermore, any element of an embodiment is meant to be combined with any and all other elements from any embodiment to describe an additional embodiment.

Definitions

The examples provided in the definitions present in this application are non-inclusive unless otherwise stated. They include but are not limited to the recited examples.

The compounds herein described may have asymmetric centers, geometric centers (e.g., double bond), or both. All chiral, diastereomeric, racemic forms and all geometric isomeric forms of a structure are intended, unless the specific stereochemistry or isomeric form is specifically indicated. Compounds of the present invention containing an asymmetrically substituted atom may be isolated in optically active or racemic forms. It is well known in the art how to prepare optically active forms, such as by resolution of racemic forms, by synthesis from optically active starting materials, or through use of chiral auxiliaries. Geometric isomers of olefins, C═N double bonds, or other types of double bonds may be present in the compounds described herein, and all such stable isomers are included in the present invention. Specifically, cis and trans geometric isomers of the compounds of the present invention may also exist and may be isolated as a mixture of isomers or as separated isomeric forms. All processes used to prepare compounds of the present invention and intermediates made therein are considered to be part of the present invention. All tautomers of shown or described compounds are also considered to be part of the present invention.

The present invention includes all isotopes of atoms occurring in the present compounds. Isotopes include those atoms having the same atomic number but different mass numbers. By way of general example and without limitation, isotopes of hydrogen include tritium and deuterium. Isotopes of carbon include C-13 and C-14.

Examples of the molecular weight of the compounds of the present invention include (a) less than about 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, or 1000 grams per mole; (b) less than about 950 grams per mole; (c) less than about 850 grams per mole; and, (d) less than about 750 grams per mole.

“Alkyl” includes both branched and straight-chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms. C₁₋₆ alkyl, for example, includes C₁, C₂, C₃, C₄, C₅, and C₆ alkyl groups. Examples of alkyl include methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl, n-pentyl, and s-pentyl.

“Alkenyl” includes the specified number of hydrocarbon atoms in either straight or branched configuration with one or more unsaturated carbon-carbon bonds that may occur in any stable point along the chain, such as ethenyl and propenyl. C₂₋₆ alkenyl includes C₂, C₃, C₄, C₅, and C₆ alkenyl groups.

“Alkynyl” includes the specified number of hydrocarbon atoms in either straight or branched configuration with one or more triple carbon-carbon bonds that may occur in any stable point along the chain, such as ethynyl and propynyl. C₂₋₆ Alkynyl includes C₂, C₃, C₄, C₅, and C₆ alkynyl groups.

“Cycloalkyl” includes the specified number of hydrocarbon atoms in a saturated ring, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. C₃₋₈ cycloalkyl includes C₃, C₄, C₅, C₆, C₇, and C₈ cycloalkyl groups.

“Alkoxy” represents an alkyl group as defined above with the indicated number of hydrocarbon atoms attached through an oxygen bridge. C₁₋₆ alkoxy, includes C₁, C₂, C₃, C₄, C₅, and C₆ alkoxy groups. Examples of alkoxy include methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, s-butoxy, t-butoxy, n-pentoxy, and s-pentoxy.

“Halo” or “halogen” refers to fluoro, chloro, bromo, and iodo.

“Counterion” is used to represent a small, negatively charged species, such as chloride, bromide, hydroxide, acetate, and sulfate.

“Aryl” refers to any stable 6, 7, 8, 9, 10, 11, 12, or 13 membered monocyclic, bicyclic, or tricyclic ring, wherein at least one ring, if more than one is present, is aromatic. Examples of aryl include fluorenyl, phenyl, naphthyl, indanyl, adamantyl, and tetrahydronaphthyl.

“Heteroaryl” refers to any stable 5, 6, 7, 8, 9, 10, 11, or 12 membered monocyclic, bicyclic, or tricyclic heterocyclic ring that is aromatic, and which consists of carbon atoms and 1, 2, 3, or 4 heteroatoms independently selected from the group consisting of N, O, and S. If the heteroaryl group is bicyclic or tricyclic, then at least one of the two or three rings must contain a heteroatom, though both or all three may each contain one or more heteroatoms. If the heteroaryl group is bicyclic or tricyclic, then only one of the rings must be aromatic. The N group may be N, NH, or N-substituent, depending on the chosen ring and if substituents are recited. The nitrogen and sulfur heteroatoms may optionally be oxidized (e.g., S, S(O), S(O)₂, and N—O). The heteroaryl ring may be attached to its pendant group at any heteroatom or carbon atom that results in a stable structure. The heteroaryl rings described herein may be substituted on carbon or on a nitrogen atom if the resulting compound is stable.

Examples of heteroaryl includes acridinyl, azocinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzoxazolinyl, benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazolinyl, carbazolyl, 4aH-carbazolyl, carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl, 2H,6H-1,5,2-dithiazinyl, dihydrofuro[2,3-b]tetrahydrofuran, furanyl, furazanyl, imidazolyl, 1H-indazolyl, indolenyl, indolinyl, indolizinyl, indolyl, 3H-indolyl, isatinoyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, naphthyridinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, oxazolidinyl, oxazolyl, oxindolyl, pyrimidinyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathinyl, phenoxazinyl, phthalazinyl, pteridinyl, pyranyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridooxazole, pyridoimidazole, pyridothiazole, pyridinyl, pyridyl, pyrimidinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, tetrazolyl, 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, thiazolyl, thienyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thiophenyl, triazinyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, and xanthenyl.

Preventing the deposition of adipose tissue covers methods of treating wherein the levels of adipose tissue of a subject remain about the same as prior to being treated in accordance with the present invention (i.e., its pre-administration level) or not more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10% greater than pre-administration level (particularly when the subject is pre-disposed to increasing adipose tissue levels).

Reversing the deposition of adipose tissue covers methods of treating wherein the levels of adipose tissue of a subject are lower than those prior to being treated in accordance with the present invention (i.e., its pre-administration level). Examples of lower include 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20% or more lower than pre-administration level.

Mammal and patient covers warm blooded mammals that are typically under medical care (e.g., humans and domesticated animals). Examples of mammals include (a) feline, canine, equine, bovine, and human and (b) human.

“Treating” or “treatment” covers the treatment of a disease-state in a mammal, and includes: (a) preventing the disease-state from occurring in a mammal, in particular, when such mammal is predisposed to the disease-state but has not yet been diagnosed as having it; (b) inhibiting the disease-state, e.g., arresting it development; and/or (c) relieving the disease-state, e.g., causing regression of the disease state until a desired endpoint is reached. Treating also includes the amelioration of a symptom of a disease (e.g., lessen the pain or discomfort), wherein such amelioration may or may not be directly affecting the disease (e.g., cause, transmission, expression, etc.).

“Pharmaceutically acceptable salts” refer to derivatives of the disclosed compounds wherein the parent compound is modified by making acid or base salts thereof. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. The pharmaceutically acceptable salts include the conventional non-toxic salts or the quaternary ammonium salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. For example, such conventional non-toxic salts include, but are not limited to, those derived from inorganic and organic acids selected from 1,2-ethanedisulfonic, 2-acetoxybenzoic, 2-hydroxyethanesulfonic, acetic, ascorbic, benzenesulfonic, benzoic, bicarbonic, carbonic, citric, edetic, ethane disulfonic, ethane sulfonic, fumaric, glucoheptonic, gluconic, glutamic, glycolic, glycollyarsanilic, hexylresorcinic, hydrabamic, hydrobromic, hydrochloric, hydroiodide, hydroxymaleic, hydroxynaphthoic, isethionic, lactic, lactobionic, lauryl sulfonic, maleic, malic, mandelic, methanesulfonic, napsylic, nitric, oxalic, pamoic, pantothenic, phenylacetic, phosphoric, polygalacturonic, propionic, salicyclic, stearic, subacetic, succinic, sulfamic, sulfanilic, sulfuric, tannic, tartaric, and toluenesulfonic.

The pharmaceutically acceptable salts of the present invention can be synthesized from the parent compound that contains a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two; generally, non-aqueous media like ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred. Lists of suitable salts are found in Remington's Pharmaceutical Sciences, 18th ed., Mack Publishing Company, Easton, Pa., 1990, p 1445, the disclosure of which is hereby incorporated by reference.

“Therapeutically effective amount” includes an amount of a compound of the present invention that is effective when administered alone or in combination to treat obesity or another indication listed herein. “Therapeutically effective amount” also includes an amount of the combination of compounds claimed that is effective to treat the desired indication. The combination of compounds is preferably a synergistic combination. Synergy, as described, for example, by Chou and Talalay, Adv. Enzyme Regul. 1984, 22:27-55, occurs when the effect of the compounds when administered in combination is greater than the additive effect of the compounds when administered alone as a single agent. In general, a synergistic effect is most clearly demonstrated at sub-optimal concentrations of the compounds. Synergy can be in terms of lower cytotoxicity, increased effect, or some other beneficial effect of the combination compared with the individual components.

Utility

Obesity is defined as having a body mass index (BMI) of 30 or above. The index is a measure of an individual's body weight relative to height. BMI is calculated by dividing body weight (in kilograms) by height (in meters) squared. Normal and healthy body weight is defined as having a BMI between 20 and 24.9. Overweight is defined as having a BMI of 25 or above. Obesity has reached epidemic proportions in the U.S., with 44 million obese Americans, and an additional eighty million deemed medically overweight.

Obesity is a disease characterized as a condition resulting from the excess accumulation of adipose tissue, especially adipose tissue localized in the abdominal area. It is desirable to treat overweight or obese patients by reducing their amount of adipose tissue, and thereby reducing their overall body weight to within the normal range for their sex and height. In this way, their risk for co-morbidities such as diabetes and cardiovascular disease will be reduced. It is also desirable to prevent normal weight individuals from accumulating additional, excess adipose tissue, effectively maintaining their body weights at a BMI<25, and preventing the development of co-morbidities. It is also desirable to control obesity, effectively preventing overweight and obese individuals from accumulating additional, excess adipose tissue, reducing the risk of further exacerbating their co-morbidities.

There exist two forms of MAO, designated MAO-A and MAO-B. The two forms differ with respect to substrate and inhibitor specificities and amino acid number and sequence. A preferred substrate for MAO-B is beta-phenylethylamine. In contrast, a preferred substrate for MAO-A is serotonin. Some MAO inhibitors show selectivity for MAO-A or for MAO-B, whereas other MAO inhibitors show little, if any selectivity. For example, the MAO inhibitor clorgyline preferentially inhibits MAO-A; the MAO inhibitor L-selegiline preferentially inhibits MAO-B; and, the MAO inhibitor iproniazid is non-selective (i.e., has a similar affinity for both). Examples of selectivity include a compound having about 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, or more fold higher affinity for one form of MAO than for the other form. One of ordinary skill in the art recognizes that there can be some difficulty in classifying MAO inhibitors. Some compounds may selectively inhibit one form of MAO in vitro and then lose their selectivity in vivo. Also, selectivity of a compound may vary from species to species or from tissue to tissue. In the context of the present invention, it is desirable to inhibit MAO-B activity in vivo in a mammal. Thus, selectivity and affinity are based on the in vivo activity of the MAO inhibitor and the mammalian species to which it is being or to be administered. Examples of the selectivity of a MAO-B inhibitor of the present invention include (a) at least a 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, to 100-fold greater affinity for MAO-B than MAO-A in the mammalian species (e.g., human) to be treated and (b) at least 100-fold greater affinity for MAO-B than MAO-A in the mammalian species (e.g., human) to be treated.

Some of the compounds of the present invention have been designed to have reduced CNS exposure by virtue of their inability or limited ability to penetrate the blood-brain barrier (e.g., quaternary salts or acid substituents) or by their participation in active transport systems, thus reducing centrally mediated side-effects, a potential problem with many anti-obesity agents.

Other compounds of the present invention are expected to penetrate the blood-brain barrier and therefore also be useful to treat CNS disorders (e.g., Parkinson's disease, depression, and Alzheimer's disease).

MAO enzymes are also located in a number of peripheral (non-CNS) tissues, including adipose tissue, muscle and liver. In order to treat non-CNS disorders (e.g., obesity, diabetes, and/or cardiometabolic disorders), it is necessary to administer enough of a drug sufficient to inhibit MAO in peripheral tissues. MAO inhibitors in use today to treat various psychiatric and neurological diseases, regardless of route of administration, enter the CNS from the systemic circulation. While present in the systemic circulation, such drugs have access to peripheral tissues, including adipose tissue, liver, and muscle. One of skill in the art recognizes that MAO inhibitors intended to enter the CNS from the systemic circulation in order to treat psychiatric and neurological diseases also have access to MAO in peripheral tissues, including adipose tissue, liver, and muscle. Thus, an MAO inhibitor useful for treating non-CNS disorders may have some access to the CNS from the systemic circulation.

Drugs enter the CNS from the systemic circulation by crossing the blood-brain barrier (BBB). The BBB is a highly specialized ‘gate-keeper’ that protects the brain by preventing the entry of many potentially harmful substances into the CNS from the systemic circulation. Much is known about the BBB, and of the physical-chemical properties required for compounds transported across it.

Drugs that do not cross the BBB into the CNS or that are readily eliminated through transport mechanisms (J Clin Invest. 97, 2517 (1996)) are known in the literature and have low CNS activity due to their inability to develop brain levels necessary for pharmacological action. The BBB has at least one mechanism to remove drugs prior to their accumulation in the CNS. P-Glycoproteins (P-gp) localized in plasma membrane of the BBB can influence the brain penetration and pharmacological activity of many drugs through translocation across membranes. The lack of accumulation into the brain by some drugs can be explained by their active removal from the brain by P-gp residing in the BBB. For example, the typical opioid drug loperamide, clinically used as an antidiarrheal, is actively removed from the brain by P-gp, thus explaining its lack of opiate-like CNS effects. Another example is domperidone, a dopamine receptor blocker that participates in the P-gp transport (J Clin Invest. 97, 2517 (1996)). Whereas dopamine receptor blockers that cross the BBB can be used to treat schizophrenia, the readily-eliminated domperidone can be used to prevent emesis, without the likelihood of producing adverse CNS effects.

In addition to the above compounds, agents possessing structural characteristics that retard or prevent BBB penetration or contribute to participation in active elimination processes have been identified in various classes of therapeutics. These include antihistamines (Drug Metab. Dispos. 31, 312 (2003)), beta-adrenergic receptor antagonists (B-blockers) (Eur. J. Clin. Pharmacol. 28, Suppl: 21-3 (1985); Br. J. Clin. Pharmacol., 11 (6), 549-553 (1981)), non-nucleoside reverse transcriptase inhibitors (NNRTIs) (J. Pharm Sci., 88(10) 950-954 (1999)), and opioid antagonists. This latter group has been tested in relation to their activity in the GI tract. These peripherally selective opioid antagonists are described in various US patents as being useful in the treatment of non-CNS pathologies in mammals, in particular those of the GI tract (see U.S. Pat. No. 5,260,542; U.S. Pat. No. 5,434,171; U.S. Pat. No. 5,159,081; and U.S. Pat. No. 5,270,238).

Other types of non-brain penetrant compounds can be prepared through the creation of a charge within the molecule. Thus, the addition of a methyl group to the tertiary amine functionality of the drugs scopolamine or atropine, unlike the parent molecules, prevents their passage across the BBB through the presence of a positive charge. However, the new molecules (methyl-scopolamine and methyl-atropine) retain their full anticholinergic pharmacological properties. As such, these drugs can also be used to treat peripheral diseases, without the concern of adverse CNS effects. The quaternary ammonium compound methylnaltrexone is also used for the prevention and/or treatment of opioid and non-opioid induced side effects associated with opioid administration.

MAO-B inhibitors such as selegiline have been useful in the treatment of CNS disorders. The unexpected discovery that the anti-obesity activity mediated by these agents is mediated by a non-CNS mechanism may make it desirable that the compounds of the present invention be peripherally restricted, i.e., have an inability or limited ability to cross the BBB or be readily eliminated from the brain through active transport systems, when a non-CNS disorder is to be treated. It may be desirable for the compounds of the present invention to be peripherally restricted, which in turn will result in no or very limited CNS effects. Compounds that provide peripherally mediated anti-obesity properties should result in therapeutic agents with greater safety, as previously demonstrated in earlier classes of peripherally restricted agents. It can be desirable that the compounds of the present invention, when administered in a therapeutically effective amount, have no or very limited CNS effects. It can also be desirable that the lack of CNS effects is a result of the compounds of the present invention having minimal brain concentrations when administered in therapeutically effective amounts. In this context, minimal brain concentrations means levels that are too low to be therapeutically effective for the treatment of a CNS indication or too low to cause significant or measurable deleterious or undesired side effects. It is noted that CNS activity is desirable when seeking to treat a CNS disorder.

Compound A is Selegiline when Y is O and R, R¹, R², X, X¹, and Z are all H. Selegiline is a drug that crosses the BBB and is indicated for the treatment of Parkinson's disease. In compound A, one of R, R¹, R², X, X¹, and Z is a group capable of reducing or limiting the CNS activity of compound A. This reduced or limited CNS activity occurs via at least one of R, R¹, R², X, X¹, and Z being a group that either limits compound A's ability to cross the BBB relative to that of Selegiline or enables it to be actively removed at a rate greater than that of Selegiline. Examples of brain levels of compound A include levels that are (a) from 50, 55, 60, 65, 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, to 100% lower than Selegiline, when administered at the same dosage; (b) from 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, to 100% lower than Selegiline, when administered at the same dosage; and, (c) from 98, 99, to 100% lower than Selegiline, when administered at the same dosage.

Most methods of treating obesity are dependent on a significant reduction in energy intake, either by a decrease in food intake (e.g., sibutramine) or by inhibition of fat absorption (e.g., orlistat). In the present invention, it can be desirable for adipose tissue to be significantly reduced in the absence of a significant reduction in food intake. The weight loss, as a result of the present invention, comes from the treatment with an MAO-B inhibitor, largely independent of appetite and food intake. Examples of the level of food intake during adipose tissue loss include (a) food intake is maintained, increased or about 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20% below the normal range of the subject prior to being treated in accordance with the present invention (i.e., its pre-administration level); (b) food intake is maintained, increased, or about 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15% below its pre-administration level; (c) food intake is maintained, increased or about 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10% below its pre-administration level; and (d) food intake level is maintained, increased or about 0, 1, 2, 3, 4, or 5% below its pre-administration level.

In some cases, loss of adipose tissue can be accompanied by a concomitant loss of lean muscle mass. This is particularly evident in cancer patients who show a wasting of all body tissue components, including adipose tissue and lean muscle mass. In the present invention, however, it can be desirable for body fat to be significantly reduced in the absence of a significant reduction in lean body mass. Adipose tissue loss comes from treatment with an MAO-B inhibitor, independent of a significant change in lean body mass. Examples of the level of lean body mass during adipose tissue loss include (a) lean body mass is maintained, increased, or is no more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30% below the normal range of the subject prior to being treated in accordance with the present invention (i.e., its pre-administration level); (b) lean body mass is maintained, increased, or is no more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15% below pre-administration levels; (c) lean body mass is maintained, increased, or is no more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10% below pre-administration levels; and (d) lean body mass is maintained, increased, or is no more than about 1, 2, 3, 4, or 5% below pre-administration levels.

In some cases, loss of adipose tissue can be accompanied by a concomitant loss of water mass. This is particularly evident with diet regimens that promote dehydration. In the present invention, it can be desirable for body fat to be significantly reduced in the absence of a significant reduction in water mass. In other words, adipose tissue loss comes from treatment with an MAO-B inhibitor, independent of a significant change in water mass. Examples of the level of water mass during adipose tissue loss include (a) water mass is maintained, increased, or is no more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30% below the normal range of the subject prior to being treated in accordance with the present invention (i.e., its pre-administration level); (b) water mass is maintained, increased, or is no more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15% below pre-administration levels; (c) water mass is maintained, increased, or is no more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10% below pre-administration levels; and (d) water mass is maintained, increased, or is no more than about 1, 2, 3, 4, or 5% below pre-administration levels.

Sibutramine and orlistat are currently marketed for use in the treatment of obesity. These two compounds achieve weight loss through entirely different mechanisms. Sibutramine, a CNS appetite suppressant, inhibits the neuronal reuptake of serotonin and noradrenaline. Orlistat inhibits gut lipase enzymes that are responsible for breaking down ingested fat.

The mechanism of action of MAO-B inhibitors is believed to be entirely different from appetite suppressants, gut lipase inhibitors, and other agents with similar indications (e.g., serotonin agonists, leptin, and fatty acid synthase inhibitors). Co-administration of a MAO-B inhibitor together with one or more other agents that are useful for treating the indications described above (e.g., obesity, diabetes, cardiometabolic disorders, and a combination thereof) is expected to be beneficial, by producing, for example, either additive or synergistic effects. Examples of additional agents include an appetite suppressant and a lipase inhibitor. Therefore, the present invention provides a method of treating obesity, diabetes, and/or cardiometabolic disorders, comprising administering a therapeutically effective amount of a compound of the present invention and a second component selected from an appetite suppressant (e.g., sibutramine, phentermine, fenfluramine) and a gut lipase inhibitor (e.g., orlistat).

MAO-B inhibitors are expected to promote weight loss without appreciably reducing caloric intake. Co-administration of an MAO-B inhibitor together with an appetite suppressant is expected to produce either additive or synergistic effects on weight loss. Similarly, co-administration of an MAO-B inhibitor together with a lipase inhibitor is expected to produce either additive or synergistic effects on weight loss.

The ability of compounds to inhibit MAOs can be determined using the method of R. Uebelhack et al., Pharmacopsychiatry 31, 187-192 (1988)(as described below).

Preparation of platelet-rich plasma and platelets. Venous blood from healthy subjects was collected between 8 and 8.30 a.m. after an overnight fast into EDTA-containing vacutainer tubes (11.6 mg EDTA/ml blood). After centrifugation of the blood at 250×g for 15 minutes at 20° C., the supernatant platelet-rich plasma (PRP) was collected and the number of platelets in PRP counted with a cell counter (MOIAB, Hilden, Germany). 2 ml of PRP was spun at 1500×g for 10 min to yield a platelet pellet. The pellet was washed three times with ice-cold saline, resuspended in 2 ml Soerensen phoshate buffer, pH 7.4 and stored at −18° C. for one day.

MAO assay. Fresh PRP or frozen platelet suspension (100 μL) was generally preincubated for 10 min in the absence or presence of drugs at 37° C. in 100 uL of 0.9% NaCl solution or phosphate buffer pH 7.4, respectively, at 37° C. 50 μL of 2-phenylethylamine-[ethyl-1-14C]hydrochloride (P EA) solution (specific activity 56 Ci/mol, Amersham) was then added in a final concentration of 5 μM, and the incubation was continued for 30 min. The reaction was terminated by the addition of 50 μL of 4M HClO₄. The reaction product of MAO, phenylacetaldehyde, was extracted into 2 mL of n-hexane. An aliquot of the organic phase was added to scintillator cocktail and the radioactivity was determined using a liquid scintillation counter. Product formation was linear with time for at least 60 min with appropriate platelet numbers. Blank values were obtained by including 2 mM pargyline in the incubation mixtures. All assays were performed in duplicate.

The ability of compounds to inhibit MAO activity can also be determined using the following method. cDNA's encoding human MAO-B can be transiently transfected into EBNA cells using the procedure described by E.-J. Schlaeger and K. Christensen (Transient Gene Expression in Mammalian Cells Grown in Serum-free Suspension Culture; Cytotechnology, 15: 1-13, 1998). After transfection, cells are homogeneized by means of a Polytron homogeneiser in 20 mM Tris HCl buffer, pH 8.0, containing 0.5 mM EGTA and 0.5 mM phenylmethanesulfonyl fluoride. Cell membranes are obtained by centrifugation at 45,000×g and, after two rinsing steps with 20 mM Tris HCl buffer, pH 8.0, containing 0.5 mM EGTA, membranes are eventually re-suspended in buffer and aliquots stored at −80° C. until use.

MAO-B enzymatic activity can be assayed using a spectrophotometric assay adapted from the method described by M. Zhou and N. Panchuk-Voloshina (A One-Step Fluorometric Method for the Continuous Measurement of Monoamine Oxidase Activity, Analytical Biochemistry, 253: 169-174, 1997). Briefly, membrane aliquots are incubated in 0.1 M potassium phosphate buffer, pH 7.4, for 30 min at 37° C. with or without various concentrations of the compounds. After incubation, the enzymatic reaction is started by the addition of the MAO substrate tyramine together with 1 U/ml horse-radish peroxidase (Roche Biochemicals) and 80 μM N-acetyl-3,7,-dihydroxyphenoxazine (Amplex Red, Molecular Probes). The samples are further incubated for 30 min at 37° C. in a final volume of 200 μl and absorbance is determined at a wavelength of 570 nm using a SpectraMax plate reader (Molecular Devices). Background (non-specific) absorbance is determined in the presence of 10 μM L-deprenyl for MAO-B. IC₅₀ values are determined from inhibition curves obtained using nine inhibitor concentrations in duplicate, by fitting data to a four parameter logistic equation.

Compounds of the present invention are expected to be MAO-B inhibitors. Representative compounds have been tested, as measured in the assay described herein, and have been shown to be active as their IC₅₀ values were found to be in the range of ≦10 μM. Compounds of the present invention are considered to be MAO-B inhibitors if they have an IC₅₀ value less than or equal to 10 μM. Additional examples of desirable activity levels of MAO-B inhibitors useful in the present invention include (a) an IC₅₀ value of 1 μM or lower, (b) an IC₅₀ value of 0.1 μM or lower, (c) an IC₅₀ value of 0.01 μM or lower, (d) an IC₅₀ value of 0.001 μM or lower, and (e) an IC₅₀ value of 0.0001 μM or lower.

In the present invention, MAO-B inhibitor(s) can be administered enterally, parenterally, orally, and transdermally. One skilled in this art is aware that the routes of administering the compounds of the present invention may vary significantly. In addition to other oral administrations, sustained release compositions may be favored. Other examples of routes include injections (e.g., intravenous, intramuscular, and intraperitoneal); subcutaneous; subdermal implants; buccal, sublingual, topical (e.g., a dermal patch), rectal, vaginal, and intranasal administrations. Bioerodible, non-bioerodible, biodegradable, and non-biodegradable systems of administration may also be used.

If a solid composition in the form of tablets is prepared, the main active ingredient can be mixed with a pharmaceutical vehicle, examples of which include silica, starch, lactose, magnesium stearate, and talc. The tablets can be coated with sucrose or another appropriate substance or they can be treated so as to have a sustained or delayed activity and so as to release a predetermined amount of active ingredient continuously. Gelatin capsules can be obtained by mixing the active ingredient with a diluent and incorporating the resulting mixture into soft or hard gelatin capsules. A syrup or elixir can contain the active ingredient in conjunction with a sweetener, which is preferably calorie-free, an antiseptic (e.g., methylparaben and/or propylparaben), a flavoring, and an appropriate color. Water-dispersible powders or granules can contain the active ingredient mixed with dispersants or wetting agents or with suspending agents such as polyvinylpyrrolidone, as well as with sweeteners or taste correctors. Rectal administration can be effected using suppositories, which are prepared with binders melting at the rectal temperature (e.g., cocoa butter and/or polyethylene glycols). Parenteral administration can be effected using aqueous suspensions, isotonic saline solutions, or injectable sterile solutions, which contain pharmacologically compatible dispersants and/or wetting agents (e.g., propylene glycol and/or polyethylene glycol). The active ingredient can also be formulated as microcapsules or microspheres, optionally with one or more carriers or additives. The active ingredient can also be presented in the form of a complex with a cyclodextrin, for example α-, β-, or γ-cyclodextrin, 2-hydroxypropyl-β-cyclodextrin, and/or methyl-β-cyclodextrin.

The dose of the MAO-B inhibitor administered daily will vary on an individual basis and to some extent may be determined by the severity of the disease being treated (e.g., obesity). The dose of the MAO-B inhibitor will also vary depending on the MAO-B inhibitor administered. An example of a range of dosages of an MAO-B inhibitor is about from 0.001, 0.002, 0.003, 0.004, 0.005, 0.006, 0.007, 0.008, 0.009, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 76, 80, 85, 90, 95, to 100 mg/kg of mammal body weight. The MAO-B inhibitor can be administered in a single dose or in a number of smaller doses over a period of time. The length of time during which the MAO-B inhibitor is administered varies on an individual basis, and can continue until the desired results are achieved (i.e., reduction of body fat, or prevention of a gain in body fat). Therapy could, therefore, last from 1 day to weeks, months, or even years depending upon the subject being treated, the desired results, and how quickly the subject responds to treatment in accordance with the present invention.

A possible example of a tablet of the present invention is as follows. Ingredient mg/Tablet Active ingredient 100 Powdered lactose 95 White corn starch 35 Polyvinylpyrrolidone 8 Na carboxymethylstarch 10 Magnesium stearate 2 Tablet weight 250

A possible example of a capsule of the present invention is as follows. Ingredient mg/Tablet Active ingredient 50 Crystalline lactose 60 Microcrystalline cellulose 34 Talc 5 Magnesium stearate 1 Capsule fill weight 150

In the above capsule, the active ingredient has a suitable particle size. The crystalline lactose and the microcrystalline cellulose are homogeneously mixed with one another, sieved, and thereafter the talc and magnesium stearate are admixed. The final mixture is filled into hard gelatin capsules of suitable size.

A possible example of an injection solution of the present invention is as follows. Ingredient mg/Tablet Active substance  1.0 mg 1 N HCl 20.0 μl acetic acid  0.5 mg NaCl  8.0 mg Phenol 10.0 mg 1 N NaOH q.s. ad pH 5 H₂O q.s. ad 1 mL Synthesis

The compounds of the present invention can be prepared in a number of ways known to one skilled in the art of organic synthesis. The compounds of the present invention can be synthesized using the methods described below, together with synthetic methods known in the art of synthetic organic chemistry, or by variations thereon as appreciated by those skilled in the art. Preferred methods include, but are not limited to, those described below. The reactions are performed in a solvent appropriate to the reagents and materials employed and suitable for the transformations being effected. It will be understood by those skilled in the art of organic synthesis that the functionality present on the molecule should be consistent with the transformations proposed. This will sometimes require a judgment to modify the order of the synthetic steps or to select one particular process scheme over another in order to obtain a desired compound of the invention. It will also be recognized that another major consideration in the planning of any synthetic route in this field is the judicious choice of the protecting group used for protection of the reactive functional groups present in the compounds described in this invention. An authoritative account describing the many alternatives to the trained practitioner is Greene and Wuts (Protective Groups In Organic Synthesis, Wiley and Sons, 1991). All references cited herein are hereby incorporated in their entirety herein by reference.

Scheme 1 provides access to one of a series of compounds that are part of the present invention. An amino acid ester, such as phenylalanine (X=H) or O-benzyltyrosine (X=O-benzyl), can be N-alkylated using formalin and sodium cyanoborohydride in the presence of acetic acid to provide an N-methylated ester (step a). Alternatively, alkylation of the amino ester with propargyl bromide in DMF at about 50° C. in the presence potassium carbonate should give the monopropargyl amino ester which can be converted to the des-methyl acid of the compound described in step e, below. When the secondary amine is treated with propargyl bromide in DMF in the presence of potassium carbonate at about 50° C., the tertiary amino ester will be produced (step b). Hydrolysis of the ester using aqueous LiOH solution in a co-solvent should afford the desired amino acid (step c). If the tertiary amino ester has a benzyloxy group on its phenyl ring, the benzyl group can be removed using trifluoroacetic acid (step d) prior to hydolysis of the ester (step e).

Alternatively, if the tertiary amino ester is reduced with lithium aluminum hydride (LAH), the primary alcohol will be produced (step f). Deprotonation of the alcohol with sodium hydride followed by alkylation with ethyl bromopropionate will afford the amino alkoxyester (step g). Treatment of this ester as in step c will yield the tertiary amino acid (step h). If the tertiary amino alkoxyester has a benzyloxy group on its phenyl ring, the benzyl group can be removed using trifluoroacetic acid prior to hydolysis of the ester.

Scheme 2 illustrates how one could make susbstituted propargyl compounds of the present invention. A starting propargyl amine can be deprotonated with n-butyl lithium at low temperature in a solvent such as THF, and the resulting anion alkylated with methylchloroformate or ethyl bromoacetate to afford an aminoester (step a). Hydrolysis of the ester using aqueous LiOH in a co-solvent can afford an amino acid (step b). Alternatively, if the tertiary amino ester has a benzyloxy group on its phenyl ring, the benzyl group can be removed using trifluoroacetic acid prior to hydrolysis of the ester.

Scheme 3 shows how to prepare hydroxy-phenyl and substituted hydroxyphenyl compounds of the present invention. A starting p-hydroxyphenethylamine can be treated with sodium hydide and the resulting phenoxide anion can be alkylated with ethyl bromoacetate to provide an ester (step a). The carboxylic acid can then be formed by the previously described hydrolysis (step b). If the alkoxide anion was alkylated with 1,3-dibromopropane, then a bromoalkylether should be produced (step c). This halide, in turn, could be treated with trimethyl amine to give the propyloxy-trimethyl ammonium salt (step d). Treatment of the hydroxyphenyl compound with formalin and dimethyl amine followed by further reaction with acetic anhydride and concentrated hydrochloric acid should yield the intermediate chloromethylated phenol (step e). Subsequent reaction with excess trimethylamine should afford the trimethylammonium salt (step f).

Scheme 4 describes the synthesis of optionally substituted benzyloxy compounds. This reaction scheme as well as the procedures found in J. Org. Chem. 1991, 56, 2395 can also be utilized to prepare substituted-biphenylmethyl analogs of this and the anilino compounds of Scheme 5 by utilizing commercially available 4′-bromomethylbiphenyl-2-carbonitrile, or for unsubstituted compounds commercially available 4-phenylbenzyl bromide, to alkylate the phenol of Scheme 4 and the anilines of Scheme 5, respectively. Treatment of the phenol with an optionally substituted benzyl bromide in a solvent such as acetone in the presence of a base such as potassium carbonate upon heating should afford the benzyl ether (step a). If the substituent on the benzyloxy group is an ester or a carbon-chain linked ester, the acid can be produced via hydrolysis using lithium hydroxide in aqueous THF (step b). If the benzyl bromide contains a nitrile subtituent or a alkyl-chain linked substituent with a nitrile group or an oxyalkyl-chain linked substituent with a nitrile group, the alkylation product (step c) can be treated with 30% hydrogen peroxide and potassium carbonate in DMSO to produce the amides (step d). Alternatively, if these nitriles are reacted with sodium azide in the presence of zinc chloride in aqueous solution or treated with trialkyltin chloride and sodium azide in refluxing toluene or xylene, followed by removal of the triakyl tin group with anhydrous HCl in THF/toluene, the tetrazoles should be formed (step e).

Scheme 5 describes the general synthesis of achiral compounds starting from substituted phenylacetones. If one uses commercially available 4-nitophenyl acetone, an anilino compound of step e that can also be used as a starting material for the reactions of Scheme 4, can be produced. Treatment of a nitro-phenyl acetone with benzylamine in the presence of sodium triacetoxyborohydride in dichloroethane (DCE) and acetic acid at 25-30° C. will yield the secondary amine (step a). Alkylation of the amine using formalin and sodium triacetoxyborohydride in DCE and HOAc at about 30° C. will provide the tertary amine (step b). Reduction of the nitro group using Fe and ammonium formate in methanol at reflux will afford the anilino compound that has also been debenzylated (step c). Alkylation of the secondary amine with propargylbromide in the presence of potassium carbonate in acetonitrile at room temperature can give the tertiary amine (step d). Treatment of this aniline with benzaldehydes in the presence of triacetoxyborohydride in DCE and HOAc will yield benzylated anilines with optionally selected substituents that can be used further for the transformations described in Scheme 4 (step e). Reaction of this aniline with methanesulfonyl chloride in the presence of a base will provide the sulfonamide derivative (step f). In addition, reaction of this aniline with acid chlorides such as ethyl malonyl chloride or 3-cyanobenzenesulfonyl chloride will produce the acetanilide or the sulfonamide, respectively.

Scheme 6 describes how one can form quarternary ammonium salts or N-oxides of the present invention. When a starting tertiary propargyl amine is treated with an alkyl halide such as propoargyl bromide in a solvent such as methanol or ethanol the quaternary ammonium salt can result (step a). Alternatively, a tertiary propargyl amine treated with an oxidizing agent such as 2-phenylsulfonyl-3-phenyloxaziridine (Davis reagent) in the presence of potassium carbonate in methylene chloride should give the amine N-oxides (step b).

Scheme 7 illustrates a route to another series of compounds that are part of the present invention. An amino acid ester, optionally substituted on the aromatic ring, can be N-alkylated using formalin and sodium cyanoborohydride under slightly acidic conditions to provide an N-methylated ester (step a). The secondary amine can then be alkylated with propargyl bromide to give a tertiary amino ester (step b). If the tertiary amino ester is reduced with lithium aluminum hydride (LAH), the primary alcohol should be produced (step c). Deprotonation of the alcohol with sodium hydride followed by alkylation with benzyl bromide should afford the amino benzyl ether (step d). Treatment of this ether with butyl lithium followed by ethyl bromoacetate should produce the acetylenic ester (step e). Hydrolysis of the ester using aqueous LiOH in a co-solvent will afford an amino acid (step f). The benzyl group can be removed using trifluoroacetic acid to give the amino acid alcohol (step g).

As shown in Scheme 8, the previously described amino alcohol (Scheme 1, step f) can be oxidized to the aldehyde using the Dess-Martin periodinane [1,1,1-tris(acetyloxy)-1,1-dihydro-1,2-benziodoxol-3-(1H)-one] in wet dichlormethane at about room temperature (step a). Treatment of the amino aldehyde with aqueous ammonia in the presence of sodium cyanoborohydride or with hydroxylamine followed by lithium aluminum hydride reduction should give the primary amine (step b). Reaction of the primary amine with methane sulfonyl chloride will afford the sulfonamide derivative (step c). The primary amine can also be reacted with ethyl 4-bromocrotonate in DMF in the presence of potassium carbonate to give the diaminoester (step d). Subsequent hydrolysis using lithium hydroxide in aqueous THF solution willl provide the diamino acid (step e). The primary amine can also be treated with ethyl malonyl chloride in the presence of pyridine to give the amide ester (step f). Subsequent treatment with lithium hydroxide in aqueous THF solution will provide the acid (step g).

Scheme 9 shows the synthesis of chiral analogs of selegiline starting from L-tyrosine methyl ester. Treatment of the ester with di-t-butyl-dicarbonate (t-Boc anhydride) in methanol in the presence of triethylamine at 40-50° C. will provide the N-t-BOC-protected ester (step a). The phenol can be alkylated with benzyl bromide or a substituted version thereof, in acetone at 50-60° C. for about 4 hours to yield the O-benzyl ether analogs (step b). The t-BOC group will then be removed with TFA in methylene chloride at room temperature for 18-20 hours (step c), and the ester can be reduced with LAH at about 60 degrees C. for 6-8 hours to afford the alcohol (step d). Protection of the amine with t-Boc anhydride in methanol in the presence of triethylamine at 40-50° C. provides the N-t-BOC-protected ester (step e). The alcohol can be converted to the iodide with iodine in the presence of triphenylphosphine and imidazole in dichloromethane at about 40-50° C. for 4-6 hours (step f). Reduction of the iodide is carried out using sodium borohydride in DMSO at about 90° C. for about 1 hour (step g). Removal of the t-BOC group with TFA in methylene chloride at room temperature for about 15-20 hours will give the amine (step h), and reductive amination using formalin, sodium triacetoxyborohydride, HOAc in dichloromethane for about 24 hours will afford the methylated amine (step i). Subsequent alkylation with propargyl bromide in the presence of potassium carbonate in acetone for about 20 hours will produce the teriary amine (step j). In Scheme 9, Bn is benzyl or benzyl optionally substituted with substituents that are compatible with LAH reduction. To produce substituted benzyl compounds with groups that are not compatible with LAH reduction, the product of step j (unsubstituted benzyl) can be de-benzylated with TFA, and the resulting phenol can be re-alkylated with benzyl halides containing various substituents on the phenyl ring.

As shown in Scheme 10, hydroxy-selegiline can be coupled with a polyethylene glycol (PEG), with one protected hydroxyl group (e.g., with a t-butyldimethylsilyl (TBDMS), alkyl, benzyl or aralkyl group), under Mitsunobu conditions using diethylazodicarboxylate (DEAD) and triphenylphosphine in a solvent (e.g., THF) to produce phenolethers (step a). The compounds with a terminal alkyl or aryl-alkyl group can be quaternized with an alkyl or propargyl halide in a variety of solvents (e.g., ether, ethanol, or toluene) to produce the quaternary ammonium salts (step b). The TBDMS-protected PEG pendants can be treated with tetrabutylammonium fluoride in THF to give the PEG pendants with terminal hydroxyl groups (step c). These alcohols can also be converted to the quaternary salts as described above (step d). The various mono-terminally substituted PEG-halides can be prepared by procedures described in Nuclear Medicine and Biology, 32, 799 (2005) or are commercially available.

Alternatively, as shown in Scheme 11, a hydroxyphenylacetic acid ester can be coupled with a halo-polyethylene glycol (PEG), optionally terminally substituted (e.g., TBDMS, alkyl, benzyl, or aryl-alkyl group), in DMF in the presence of potassium carbonate at about 100° C. with stirring for 12-16 hours to afford the PEG ether ester (step a). After hydrolysis of the ester with lithium hydroxide in aqueous THF, the resultant acid can converted to the acid chloride upon heating in oxalyl chloride (step b). Treatment of the acid chloride with 2,2-dimethyl-1,3-dioxane-4,6-dione (Meldrum's acid) should produce the acylated anhydride (step c), and subsequent hydrolysis in aqueous acetic acid will provide the methyl ketone (step d). Reductive amination of the ketone with methylpropargylamine in the presence of sodium triacetoxyborohydride in dichloroethane and acetic acid should afford the amine (step e). The compounds with a terminal alkyl or aryl-alkyl group can be quaternized with alkyl or propargyl halides in a variety of solvents such as ether, ethanol, or toluene to produce the quaternary ammonium salts (step f). The TBDMS-protected PEG pendants can be treated with tetrabutylammonium fluoride in THF to give the PEG pendants with terminal hydroxyl groups (step g). These alcohols can also be converted to the quaternary salts as described above (step h).

One stereoisomer of a compound of the present invention may be a more potent MAO-B inhibitor than its counterpart(s). Thus, stereoisomers are included in the present invention. Some of these stereoisomers are shown below in Scheme 12. When required, separation of the racemic material can be achieved by HPLC using a chiral column or by a resolution using a resolving agent such as described in Wilen, S. H. Tables of Resolving Agents and Optical Resolutions 1972, 308 or using enantiomerically pure acids and bases. A chiral compound of the present invention may also be directly synthesized using a chiral catalyst or a chiral ligand, e.g., Jacobsen, E. Acc. Chem. Res. 2000, 33, 421-431 or using other enantio- and diastereo-selective reactions and reagents known to one skilled in the art of asymmetric synthesis.

Other features of the invention will become apparent in the course of the following descriptions of exemplary embodiments that are given for illustration of the invention and are not intended to be limiting thereof.

EXAMPLES

Tables A and B below describe examples of the present invention that have been prepared. The examples can be prepared according to the methods of the scheme numbers provided for each example.

For X, the number in the parentheses indicates the substituent's position on phenyl ring in the X group. TABLE A

NMR Ex # X Y Z (Solvent) Scheme 1 OCH₂C₆H₅ H₂ H (CDCl₃) 4,9 CH₃: 0.97(d) C≡CH: 2.25(m) PhCH: 2.35(m) NCH₃: 2.43(s) PhCH: 2.96(m) NCH: 3.01(m) NCH₂: 3.44(m) PhCH₂O: 5.04(s) aromatic H's 6.89-7.44 2 OCH₂C₆H₄— H₂ H (CDCl₃) 4 CO₂CH₃(3) CH₃: 0.98(d) C≡CH: 2.27(m) PhCH: 2.36(m) NCH₃: 2.44(s) PhCH: 2.93(m) NCH: 3.00(m) NCH₂: 3.45(q) OCH₃: 3.93(s) PhCH₂O: 5.08(s) aromatic H's 6.89-8.11 3 OCH₂C₆H₄— H₂ H (CDCl₃) 4 CONH₂(4) CH₃: 1.00(d) C≡CH: 2.17(m) PhCH: 2.30(m) NCH₃: 2.47(s) PhCH: 3.00(m) NCH: 3.00(m) NCH₂: 3.48(m) OCH₃: 3.92(s) PhCH₂O: 5.11(s) aromatic H's 6.89, 7.10, 7.52, 7.84 d's 4 OCH₂C₆H₄— H₂ H (CD₃OD) 4 CONH₂(3) CH₃: 0.98(d) PhCH: 2.34(m) NCH₃: 2.41(s) C≡CH: 2.70(m) PhCH: 3.00(m) NCH: 3.00(m) NCH₂: 3.45(m) PhCH₂O: 5.12(s) aromatic H's 6.93-7.97 5 OCH₂CH═CH— H₂ H (CDCl₃) 3 CO₂CH₂CH₃ CH₃: 0.96(d) ester-CH₃: 1.30(t) C≡CH: 2.25(m) PhCH: 2.35(m) NCH₃: 2.42(s) PhCH: 2.95(m) NCH: 2.99(m) NCH₂: 3.43(q) OCH₂: 4.22(q) OCH₂vinyl: 4.68(m) CH═: 6.19(dt) CH═: 7.06(dt) C₆H₄: 6.83, 7.09(dd) 6 OCH₂C₆H₅ O OCH₃ (CDCl₃) 1 N—CH₃═N—H C≡CH: 2.17(m) in structure at top PhCH₂: 2.93(dq) of table NCH₂: 3.39(dq) OCH₃: 3.67(s) NCH: 3.70(m) PhCH₂O: 5.03(s) aromatic H's 6.89-7.40 7 OCH₂C₆H₄— H₂ H (CD₃OD) 4 OCH₂CONH₂ CH₃: 0.96(d) (3) PhCH: 2.35(m) NCH₃: 2.42(s) C≡CH: 2.70(m) PhCH: 2.99(m) NCH₂: 3.46(m) PhCH₂CO: 3.54(s) PhCH₂O: 5.05(s) aromatic H's 6.90-7.41 8 OCH₂C₆H₄— H₂ H (CD₃OD) 4 CH₂CONH₂(3) CH₃: 0.96(d) PhCH: 2.33(m) NCH₃: 2.40(s) C≡CH: 2.70(m) PhCH: 3.00(m) NCH₂: 3.48(m) OCH₂CO: 4.50(s) PhCH₂O: 5.04(s) aromatic H's 6.90-7.33 9 H H₂ OH (CDCl₃) 1 C≡CH: 2.28(m) NCH₃: 2.42(s) NCH, PhCH: 3.09(m) NCH₂, 3.38(m) CH₂O: 3.43(d) aromatic H's 7.15-7.30 10 OCH₂C₆H₅ H₂ OH (CDCl₃) 1 C≡CH: 2.30(m) PhCH: 2.35(t) NCH₃: 2.45(s) PhCH: 3.01(m) NCH: 3.04(m) NCH₂, 3.40(m) CH₂O: 3.47(d) PhCH₂O: 5.04(s) aromatic H's 6.89-7.44 11 OCH₂C₆H₅ O OCH₃ (CDCl₃) 1 C≡CH: 2.27(m) NCH₃: 2.46(s) PhCH₂: 2.97(d) NCH₂: 3.50(dq) OCH₃: 3.57(s) NCH: 3.58(m) PhCH₂O: 5.03(s) aromatic H's 6.88-7.41 12 NO₂ H₂ H (CDCl₃) 5 CH₃: 1.00(d) C≡CH: 2.26(m) PhCH: 2.58(m) NCH₃: 2.41(s) PhCH: 3.05(m) NCH: 3.05(m) NCH₂: 3.42(q) aromatic H's: 7.34, 7.36, 8.14, 8.16 13 OCH₂C₆H₄CH₃ H₂ H (CDCl₃) 4,9 (3) CH₃: 0.97(d) C≡CH: 2.24(m) PhCH: 2.36(m) PhCH₃: 2.37(s) NCH₃: 2.42(s) PhCH: 2.97(m) NCH: 3.05(m) NCH₂: 3.43(q) PhCH₂O: 5.00(s) aromatic H's: 6.89-7.29 14 OCH₂C₆H₄CF₃ H₂ H (CDCl₃) 4,9 (3) CH₃: 0.99(d) C≡CH: 2.27(m) PhCH: 2.38(m) NCH₃: 2.45(s) PhCH: 2.97(m) NCH: 3.00(m) NCH₂: 3.47(q) PhCH₂O: 5.09(s) aromatic H's: 6.89-7.63 15 OCH₂C₆H₄CH₃ H₂ H (CDCl₃) 4,9 (4) CH₃: 0.96(d) C═CH: 2.24(m) PhCH: 2.35(m) PhCH₃: 2.36(s) NCH₃: 2.42(s) PhCH: 2.95(m) NCH: 2.97(m) NCH₂: 3.42(q) PhCH₂O: 4.99(s) aromatic H's: 6.88-7.32 16 OCH₂C₆H₄CN H₂ H (CDCl₃) 4,9 (3) CH₃: 0.97(d) C≡CH: 2.26(m) PhCH: 2.38(m) NCH₃: 2.43(s) PhCH: 2.97(m) NCH: 2.99(m) NCH₂: 3.44(q) PhCH₂O: 5.07(s) aromatic H's: 6.87-7.65 17 NHCH₂C₆H₄CN H₂ H (CDCl₃) 5 (4) CH₃: 0.97(d) C≡CH: 2.22(m) PhCH: 2.27(m) NCH₃: 2.39(s) PhCH: 2.86(m) NCH: 2.91(m) NCH₂:3.40(g) PhCH₂N: 4.39(s) aromatic H's: 6.50(d), 6.97(d), 7.47(d), 7.60(d) 18 NHCH₂C₆H₄OH H₂ H (CDCl₃) 5 (4) CH₃: 0.96(d) C≡CH: 2.24(m) PhCH: 2.27(m) NCH₃: 2.42(s) PhCH: 2.86(m) NCH: 2.91(m) NCH₂: 3.43(q) PhCH₂N: 4.21(s) aromatic H's: 6.57(d), 6.80(d), 6.97(d), 7.23(d) 19 NHCH₂C₆H₄OH H₂ H (CDCl₃) 5 (3) CH₃: 0.95(d) C≡CH: 2.23(m) PhCH: 2.28(m) NCH₃: 2.41(s) PhCH: 2.89(m) NCH: 2.92(m) NCH₂: 3.42(q) PhCH₂N: 4.26(s) aromatic H's: 6.53-7.20

TABLE B

NMR Ex # X R Q (Solvent) Scheme 1 H CH₃ CH₂C≡CH (CD₃OD) 6 CH₃(d) 1.40 NCH₃(s) 3.30 CH(m) 4.20 NCH₂(m) 4.70 C₆H₅: 7.33-7.44 2 OCH₂C₆H₅ CH₃ CH₂C≡CH (CD₃OD) 6 CH₃: 1.34(d) PhCH: 2.74(t) NCH₃: 3.25 s C≡CH: 3.30(m) PhCH: 3.43(d) CH: 4.07(m) NCH₂: 4.64(m) PhCH₂O: 5.08(s) C₆H₄: 7.00, 7.21 (dd), C₆H₅: 7.30-7.44 3 OCH₂C₆H₅ CH₃ CH₃ (CD₃OD) 6 CH₃: 1.30(d) PhCH: 2.67(t) NCH₃: 3.22(s) C≡CH: 3.30(m) PhCH: 3.40(d) CH: 3.90(m) NCH₂: 4.51(q) PhCH₂O: 5.07(s) 7.99, 7.21(dd) C₆H₅: 7.27-7.43

Tables I-Xb show representative examples of the compounds of the present invention. Each example in each table represents an individual species of the present invention. TABLE I

Ex. # X X¹ R R¹ 1 H H CH₃ H 2 H H H H 3 H H CH₃ CH₃ 4 H H H CH₃ 5 OH H CH₃ H 6 OH H H H 7 OH H CH₃ CH₃ 8 OH H H CH₃ 9 OCH₃ H CH₃ H 10 OCH₃ H H H 11 OCH₃ H CH₃ CH₃ 12 OCH₃ H H CH₃ 13 OCH₂C₆H₅ H CH₃ H 14 OCH₂C₆H₅ H H H 15 OCH₂C₆H₅ H CH₃ CH₃ 16 OCH₂C₆H₅ H H CH₃ 17 OCH₂CH₂C₆H₅ H CH₃ H 18 OCH₂CH₂C₆H₅ H H H 19 OCH₂CH₂C₆H₅ H CH₃ CH₃ 20 OCH₂CH₂C₆H₅ H H CH₃ 21 OCH₂CH═CH₂ H CH₃ H 22 OCH₂CH═CH₂ H H H 23 OCH₂CH═CH₂ H CH₃ CH₃ 24 OCH₂CH═CH₂ H H CH₃ 25 OCH₂CONH₂ H CH₃ H 26 OCH₂CONH₂ H H H 27 OCH₂CONH₂ H CH₃ CH₃ 28 OCH₂CONH₂ H H CH₃ 29 Cl H CH₃ H 30 Cl H H H 31 Cl H CH₃ CH₃ 32 Cl H H CH₃ 33 NO₂ H CH₃ H 34 NO₂ H H H 35 NO₂ H CH₃ CH₃ 36 NO₂ H H CH₃ 37 NH₂ H CH₃ H 38 NH₂ H H H 39 NH₂ H CH₃ CH₃ 40 NH₂ H H CH₃ 41 NHSO₂CH₃ H CH₃ H 42 NHSO₂CH₃ H H H 43 NHSO₂CH₃ H CH₃ CH₃ 44 NHSO₂CH₃ H H CH₃ 45 OH CH₂N(CH₃)₂ CH₃ H 46 OH CH₂N(CH₃)₂ H H 47 OH CH₂N(CH₃)₂ CH₃ CH₃ 48 OH CH₂N(CH₃)₂ H CH₃ 49 OH CH₂N⁻(CH₃)₃Cl⁻ CH₃ H 50 OH CH₂N⁻(CH₃)₃Cl⁻ H H 51 OH CH₂N⁻(CH₃)₃Cl⁻ CH₃ CH₃ 52 OH CH₂N⁻(CH₃)₃Cl⁻ H CH₃ 53 OCH₃ CH₂N(CH₃)₂ CH₃ H 54 OCH₃ CH₂N(CH₃)₂ H H 55 OCH₃ CH₂N(CH₃)₂ CH₃ CH₃ 56 OCH₃ CH₂N(CH₃)₂ H CH₃ 57 OCH₃ CH₂N⁻(CH₃)₃Cl⁻ CH₃ H 58 OCH₃ CH₂N⁻(CH₃)₃Cl⁻ H H 59 OCH₃ CH₂N⁻(CH₃)₃Cl⁻ CH₃ CH₃ 60 OCH₃ CH₂N⁻(CH₃)₃Cl⁻ H CH₃

TABLE II

Ex. # X X¹ R¹ 1 H H CO₂CH₂CH₃ 2 H H CO₂H 3 OH H CO₂CH₂CH₃ 4 OH H CO₂H 5 OCH₃ H CO₂CH₂CH₃ 6 OCH₃ H CO₂H 7 OCH₂CH═CH₂ H CO₂CH₂CH₃ 8 OCH₂CH═CH₂ H CO₂H 9 OCH₂C₆H₅ H CO₂CH₂CH₃ 10 OCH₂C₆H₅ H CO₂H 11 OCH₂CH₂C₆H₅ H CO₂CH₂CH₃ 12 OCH₂CH₂C₆H₅ H CO₂H 13 OCH₂CONH₂ H CO₂CH₂CH₃ 14 OCH₂CONH₂ H CO₂H 15 Cl H CO₂CH₂CH₃ 16 Cl H CO₂H 17 NO₂ H CO₂CH₂CH₃ 18 NO₂ H CO₂H 19 NH₂ H CO₂CH₂CH₃ 20 NH₂ H CO₂H 21 NHSO₂CH₃ H CO₂CH₂CH₃ 22 NHSO₂CH₃ H CO₂H 23 OH CH₂N(CH₃)₂ CO₂CH₂CH₃ 24 OH CH₂N(CH₃)₂ CO₂H 25 OCH₃ CH₂N(CH₃)₂ CO₂CH₂CH₃ 26 OCH₃ CH₂N(CH₃)₂ CO₂H 27 OCH₂C₆H₅ CH₂N(CH₃)₂ CO₂CH₂CH₃ 28 OCH₂C₆H₅ CH₂N(CH₃)₂ CO₂H 29 OH CH₂N⁻(CH₃)₃Cl⁻ CO₂CH₂CH₃ 30 OH CH₂N⁻(CH₃)₃Cl⁻ CO₂H 31 OCH₃ CH₂N⁻(CH₃)₃Cl⁻ CO₂CH₂CH₃ 32 OCH₃ CH₂N⁻(CH₃)₃Cl⁻ CO₂H 33 OCH₂C₆H₅ CH₂N⁻(CH₃)₃Cl⁻ CO₂CH₂CH₃ 34 OCH₂C₆H₅ CH₂N⁻(CH₃)₃Cl⁻ CO₂H 35 H H CH₂CO₂CH₂CH₃ 36 H H CH₂CO₂H 37 OH H CH₂CO₂CH₂CH₃ 38 OH H CH₂CO₂H 39 OCH₃ H CH₂CO₂CH₂CH₃ 40 OCH₃ H CH₂CO₂H 41 OCH₂CH═CH₂ H CH₂CO₂CH₂CH₃ 42 OCH₂CH═CH₂ H CH₂CO₂H 43 OCH₂C₆H₅ H CH₂CO₂CH₂CH₃ 44 OCH₂C₆H₅ H CH₂CO₂H 45 OCH₂CH₂C₆H₅ H CH₂CO₂CH₂CH₃ 46 OCH₂CH₂C₆H₅ H CH₂CO₂H 47 OCH₂CONH₂ H CH₂CO₂CH₂CH₃ 48 OCH₂CONH₂ H CH₂CO₂H 49 Cl H CH₂CO₂CH₂CH₃ 50 Cl H CH₂CO₂H 51 NO₂ H CH₂CO₂CH₂CH₃ 52 NO₂ H CH₂CO₂H 53 NH₂ H CH₂CO₂CH₂CH₃ 54 NH₂ H CH₂CO₂H 55 NHSO₂CH₃ H CH₂CO₂CH₂CH₃ 56 NHSO₂CH₃ H CH₂CO₂H 57 OH CH₂N(CH₃)₂ CH₂CO₂CH₂CH₃ 58 OH CH₂N(CH₃)₂ CH₂CO₂H 59 OCH₃ CH₂N(CH₃)₂ CH₂CO₂CH₂CH₃ 60 OCH₃ CH₂N(CH₃)₂ CH₂CO₂H 61 OCH₂C₆H₅ CH₂N(CH₃)₂ CH₂CO₂CH₂CH₃ 62 OCH₂C₆H₅ CH₂N(CH₃)₂ CH₂CO₂H 63 OH CH₂N⁻(CH₃)₃Cl⁻ CH₂CO₂CH₂CH₃ 64 OH CH₂N⁻(CH₃)₃Cl⁻ CH₂CO₂H 65 OCH₃ CH₂N⁻(CH₃)₃Cl⁻ CH₂CO₂CH₂CH₃ 66 OCH₃ CH₂N⁻(CH₃)₃Cl⁻ CH₂CO₂H 67 OCH₂C₆H₅ CH₂N⁻(CH₃)₃Cl⁻ CH₂CO₂CH₂CH₃ 68 OCH₂C₆H₅ CH₂N⁻(CH₃)₃Cl⁻ CH₂CO₂H 69 H H CH₂CH₂CO₂CH₂CH₃ 70 H H CH₂CH₂CO₂H 71 OH H CH₂CH₂CO₂CH₂CH₃ 72 OH H CH₂CH₂CO₂H 73 OCH₃ H CH₂CH₂CO₂CH₂CH₃ 74 OCH₃ H CH₂CH₂CO₂H 75 OCH₂CH═CH₂ H CH₂CH₂CO₂CH₂CH₃ 76 OCH₂CH═CH₂ H CH₂CH₂CO₂H 77 OCH₂C₆H₅ H CH₂CH₂CO₂CH₂CH₃ 78 OCH₂C₆H₅ H CH₂CH₂CO₂H 79 OCH₂CH₂C₆H₅ H CH₂CH₂CO₂CH₂CH₃ 80 OCH₂CH₂C₆H₅ H CH₂CH₂CO₂H 81 OCH₂CONH₂ H CH₂CH₂CO₂CH₂CH₃ 82 OCH₂CONH₂ H CH₂CH₂CO₂H 83 Cl H CH₂CH₂CO₂CH₂CH₃ 84 Cl H CH₂CH₂CO₂H 85 NO₂ H CH₂CH₂CO₂CH₂CH₃ 86 NO₂ H CH₂CH₂CO₂H 87 NH₂ H CH₂CH₂CO₂CH₂CH₃ 88 NH₂ H CH₂CH₂CO₂H 89 NHSO₂CH₃ H CH₂CH₂CO₂CH₂CH₃ 90 NHSO₂CH₃ H CH₂CH₂CO₂H 91 OH CH₂N(CH₃)₂ CH₂CH₂CO₂CH₂CH₃ 92 OH CH₂N(CH₃)₂ CH₂CH₂CO₂H 93 OCH₃ CH₂N(CH₃)₂ CH₂CH₂CO₂CH₂CH₃ 94 OCH₃ CH₂N(CH₃)₂ CH₂CH₂CO₂H 95 OCH₂C₆H₅ CH₂N(CH₃)₂ CH₂CH₂CO₂CH₂CH₃ 96 OCH₂C₆H₅ CH₂N(CH₃)₂ CH₂CH₂CO₂H 97 OH CH₂N⁻(CH₃)₃Cl⁻ CH₂CH₂CO₂CH₂CH₃ 98 OH CH₂N⁻(CH₃)₃Cl⁻ CH₂CH₂CO₂H 99 OCH₃ CH₂N⁻(CH₃)₃Cl⁻ CH₂CH₂CO₂CH₂CH₃ 100 OCH₃ CH₂N⁻(CH₃)₃Cl⁻ CH₂CH₂CO₂H 101 OCH₂C₆H₅ CH₂N⁻(CH₃)₃Cl⁻ CH₂CH₂CO₂CH₂CH₃ 102 OCH₂C₆H₅ CH₂N⁻(CH₃)₃Cl⁻ CH₂CH₂CO₂H 103 H H CH₂CH═CHCO₂CH₂CH₃ 104 H H CH₂CH═CHCO₂H 105 OH H CH₂CH═CHCO₂CH₂CH₃ 106 OH H CH₂CH═CHCO₂H 107 OCH₃ H CH₂CH═CHCO₂CH₂CH₃ 108 OCH₃ H CH₂CH═CHCO₂H 109 OCH₂CH═CH₂ H CH₂CH═CHCO₂CH₂CH₃ 110 OCH₂CH═CH₂ H CH₂CH═CHCO₂H 111 OCH₂C₆H₅ H CH₂CH═CHCO₂CH₂CH₃ 112 OCH₂C₆H₅ H CH₂CH═CHCO₂H 113 OCH₂CH₂C₆H₅ H CH₂CH═CHCO₂CH₂CH₃ 114 OCH₂CH₂C₆H₅ H CH₂CH═CHCO₂H 115 OCH₂CONH₂ H CH₂CH═CHCO₂CH₂CH₃ 116 OCH₂CONH₂ H CH₂CH═CHCO₂H 117 Cl H CH₂CH═CHCO₂CH₂CH₃ 118 Cl H CH₂CH═CHCO₂H 119 NO₂ H CH₂CH═CHCO₂CH₂CH₃ 120 NO₂ H CH₂CH═CHCO₂H 121 NH₂ H CH₂CH═CHCO₂CH₂CH₃ 122 NH₂ H CH₂CH═CHCO₂H 123 NHSO₂CH₃ H CH₂CH═CHCO₂CH₂CH₃ 124 NHSO₂CH₃ H CH₂CH═CHCO₂H 125 OH CH₂N(CH₃)₂ CH₂CH═CHCO₂CH₂CH₃ 126 OH CH₂N(CH₃)₂ CH₂CH═CHCO₂H 127 OCH₃ CH₂N(CH₃)₂ CH₂CH═CHCO₂CH₂CH₃ 128 OCH₃ CH₂N(CH₃)₂ CH₂CH═CHCO₂H 129 OCH₂C₆H₅ CH₂N(CH₃)₂ CH₂CH═CHCO₂CH₂CH₃ 130 OCH₂C₆H₅ CH₂N(CH₃)₂ CH₂CH═CHCO₂H 131 OH CH₂N⁻(CH₃)₃Cl⁻ CH₂CH═CHCO₂CH₂CH₃ 132 OH CH₂N⁻(CH₃)₃Cl⁻ CH₂CH═CHCO₂H 133 OCH₃ CH₂N⁻(CH₃)₃Cl⁻ CH₂CH═CHCO₂CH₂CH₃ 134 OCH₃ CH₂N⁻(CH₃)₃Cl⁻ CH₂CH═CHCO₂H 135 OCH₂C₆H₅ CH₂N⁻(CH₃)₃Cl⁻ CH₂CH═CHCO₂CH₂CH₃ 136 OCH₂C₆H₅ CH₂N⁻(CH₃)₃Cl⁻ CH₂CH═CHCO₂H 137 H H CH₂CH₂PO(OCH₂CH₃)₂ 138 H H CH₂CH₂PO(OH)₂ 139 OH H CH₂CH₂PO(OCH₂CH₃)₂ 140 OH H CH₂CH₂PO(OH)₂ 141 OCH₃ H CH₂CH₂PO(OCH₂CH₃)₂ 142 OCH₃ H CH₂CH₂PO(OH)₂ 143 OCH₂CH═CH₂ H CH₂CH₂PO(OCH₂CH₃)₂ 144 OCH₂CH═CH₂ H CH₂CH₂PO(OH)₂ 145 OCH₂C₆H₅ H CH₂CH₂PO(OCH₂CH₃)₂ 146 OCH₂C₆H₅ H CH₂CH₂PO(OH)₂ 147 OCH₂CH₂C₆H₅ H CH₂CH₂PO(OCH₂CH₃)₂ 148 OCH₂CH₂C₆H₅ H CH₂CH₂PO(OH)₂ 149 OCH₂CONH₂ H CH₂CH₂PO(OCH₂CH₃)₂ 150 OCH₂CONH₂ H CH₂CH₂PO(OH)₂ 151 Cl H CH₂CH₂PO(OCH₂CH₃)₂ 152 Cl H CH₂CH₂PO(OH)₂ 153 NO₂ H CH₂CH₂PO(OCH₂CH₃)₂ 154 NO₂ H CH₂CH₂PO(OH)₂ 155 NH₂ H CH₂CH₂PO(OCH₂CH₃)₂ 156 NH₂ H CH₂CH₂PO(OH)₂ 157 NHSO₂CH₃ H CH₂CH₂PO(OCH₂CH₃)₂ 158 NHSO₂CH₃ H CH₂CH₂PO(OH)₂ 159 OH CH₂N(CH₃)₂ CH₂CH₂PO(OCH₂CH₃)₂ 160 OH CH₂N(CH₃)₂ CH₂CH₂PO(OH)₂ 161 OCH₃ CH₂N(CH₃)₂ CH₂CH₂PO(OCH₂CH₃)₂ 162 OCH₃ CH₂N(CH₃)₂ CH₂CH₂PO(OH)₂ 163 OCH₂C₆H₅ CH₂N(CH₃)₂ CH₂CH₂PO(OCH₂CH₃)₂ 164 OCH₂C₆H₅ CH₂N(CH₃)₂ CH₂CH₂PO(OH)₂ 165 OH CH₂N⁻(CH₃)₃Cl⁻ CH₂CH₂PO(OCH₂CH₃)₂ 166 OH CH₂N⁻(CH₃)₃Cl⁻ CH₂CH₂PO(OH)₂ 167 OCH₃ CH₂N⁻(CH₃)₃Cl⁻ CH₂CH₂PO(OCH₂CH₃)₂ 168 OCH₃ CH₂N⁻(CH₃)₃Cl⁻ CH₂CH₂PO(OH)₂ 169 OCH₂C₆H₅ CH₂N⁻(CH₃)₃Cl⁻ CH₂CH₂PO(OCH₂CH₃)₂ 170 OCH₂C₆H₅ CH₂N⁻(CH₃)₃Cl⁻ CH₂CH₂PO(OH)₂

TABLE IIIa

Ex. # X X¹ Z¹ R¹ 1 H H CH₂CO₂CH₂CH₃ H 2 H H CH₂CO₂H H 3 H H CH₂CO₂CH₂CH₃ CH₃ 4 H H CH₂CO₂H CH₃ 5 OH H CH₂CO₂CH₂CH₃ H 6 OH H CH₂CO₂H H 7 OH H CH₂CO₂CH₂CH₃ CH₃ 8 OH H CH₂CO₂H CH₃ 9 OCH₃ H CH₂CO₂CH₂CH₃ H 10 OCH₃ H CH₂CO₂H H 11 OCH₃ H CH₂CO₂CH₂CH₃ CH₃ 12 OCH₃ H CH₂CO₂H CH₃ 13 OCH₂C₆H₅ H CH₂CO₂CH₂CH₃ H 14 OCH₂C₆H₅ H CH₂CO₂H H 15 OCH₂C₆H₅ H CH₂CO₂CH₂CH₃ CH₃ 16 OCH₂C₆H₅ H CH₂CO₂H CH₃ 17 OCH₂CH₂C₆H₅ H CH₂CO₂CH₂CH₃ H 18 OCH₂CH₂C₆H₅ H CH₂CO₂H H 19 OCH₂CH₂C₆H₅ H CH₂CO₂CH₂CH₃ CH₃ 20 OCH₂CH₂C₆H₅ H CH₂CO₂H CH₃ 21 OCH₂CH═CH₂ H CH₂CO₂CH₂CH₃ H 22 OCH₂CH═CH₂ H CH₂CO₂H H 23 OCH₂CH═CH₂ H CH₂CO₂CH₂CH₃ CH₃ 24 OCH₂CH═CH₂ H CH₂CO₂H CH₃ 25 OCH₂CONH₂ H CH₂CO₂CH₂CH₃ H 26 OCH₂CONH₂ H CH₂CO₂H H 27 OCH₂CONH₂ H CH₂CO₂CH₂CH₃ CH₃ 28 OCH₂CONH₂ H CH₂CO₂H CH₃ 29 Cl H CH₂CO₂CH₂CH₃ H 30 Cl H CH₂CO₂H H 31 Cl H CH₂CO₂CH₂CH₃ CH₃ 32 Cl H CH₂CO₂H CH₃ 33 NO₂ H CH₂CO₂CH₂CH₃ H 34 NO₂ H CH₂CO₂H H 35 NO₂ H CH₂CO₂CH₂CH₃ CH₃ 36 NO₂ H CH₂CO₂H CH₃ 37 NH₂ H CH₂CO₂CH₂CH₃ H 38 NH₂ H CH₂CO₂H H 39 NH₂ H CH₂CO₂CH₂CH₃ CH₃ 40 NH₂ H CH₂CO₂H CH₃ 41 NHSO₂CH₃ H CH₂CO₂CH₂CH₃ H 42 NHSO₂CH₃ H CH₂CO₂H H 43 NHSO₂CH₃ H CH₂CO₂CH₂CH₃ CH₃ 44 NHSO₂CH₃ H CH₂CO₂H CH₃ 45 OH CH₂N(CH₃)₂ CH₂CO₂CH₂CH₃ H 46 OH CH₂N(CH₃)₂ CH₂CO₂H H 47 OH CH₂N(CH₃)₂ CH₂CO₂CH₂CH₃ CH₃ 48 OH CH₂N(CH₃)₂ CH₂CO₂H CH₃ 49 OH CH₂N⁺(CH₃)₃Cl⁻ CH₂CO₂CH₂CH₃ H 50 OH CH₂N⁺(CH₃)₃Cl⁻ CH₂CO₂H H 51 OH CH₂N⁺(CH₃)₃Cl⁻ CH₂CO₂CH₂CH₃ CH₃ 52 OH CH₂N⁺(CH₃)₃Cl⁻ CH₂CO₂H CH₃ 53 OCH₃ CH₂N(CH₃)₂ CH₂CO₂CH₂CH₃ H 54 OCH₃ CH₂N(CH₃)₂ CH₂CO₂H H 55 OCH₃ CH₂N(CH₃)₂ CH₂CO₂CH₂CH₃ CH₃ 56 OCH₃ CH₂N(CH₃)₂ CH₂CO₂H CH₃ 57 OCH₃ CH₂N⁺(CH₃)₃Cl⁻ CH₂CO₂CH₂CH₃ H 58 OCH₃ CH₂N⁺(CH₃)₃Cl⁻ CH₂CO₂H H 59 OCH₃ CH₂N⁺(CH₃)₃Cl⁻ CH₂CO₂CH₂CH₃ CH₃ 60 OCH₃ CH₂N⁺(CH₃)₃Cl⁻ CH₂CO₂H CH₃ 61 H H CH₂CH₂CO₂CH₂CH₃ H 62 H H CH₂CH₂CO₂H H 63 H H CH₂CH₂CO₂CH₂CH₃ CH₃ 64 H H CH₂CH₂CO₂H CH₃ 65 OH H CH₂CH₂CO₂CH₂CH₃ H 66 OH H CH₂CH₂CO₂H H 67 OH H CH₂CH₂CO₂CH₂CH₃ CH₃ 68 OH H CH₂CH₂CO₂H CH₃ 69 OCH₃ H CH₂CH₂CO₂CH₂CH₃ H 70 OCH₃ H CH₂CH₂CO₂H H 71 OCH₃ H CH₂CH₂CO₂CH₂CH₃ CH₃ 72 OCH₃ H CH₂CH₂CO₂H CH₃ 73 OCH₂C₆H₅ H CH₂CH₂CO₂CH₂CH₃ H 74 OCH₂C₆H₅ H CH₂CH₂CO₂H H 75 OCH₂C₆H₅ H CH₂CH₂CO₂CH₂CH₃ CH₃ 76 OCH₂C₆H₅ H CH₂CH₂CO₂H CH₃ 77 OCH₂CH₂C₆H₅ H CH₂CH₂CO₂CH₂CH₃ H 78 OCH₂CH₂C₆H₅ H CH₂CH₂CO₂H H 79 OCH₂CH₂C₆H₅ H CH₂CH₂CO₂CH₂CH₃ CH₃ 80 OCH₂CH₂C₆H₅ H CH₂CH₂CO₂H CH₃ 81 OCH₂CH═CH₂ H CH₂CH₂CO₂CH₂CH₃ H 82 OCH₂CH═CH₂ H CH₂CH₂CO₂H H 83 OCH₂CH═CH₂ H CH₂CH₂CO₂CH₂CH₃ CH₃ 84 OCH₂CH═CH₂ H CH₂CH₂CO₂H CH₃ 85 OCH₂CONH₂ H CH₂CH₂CO₂CH₂CH₃ H 86 OCH₂CONH₂ H CH₂CH₂CO₂H H 87 OCH₂CONH₂ H CH₂CH₂CO₂CH₂CH₃ CH₃ 88 OCH₂CONH₂ H CH₂CH₂CO₂H CH₃ 89 Cl H CH₂CH₂CO₂CH₂CH₃ H 90 Cl H CH₂CH₂CO₂H H 91 Cl H CH₂CH₂CO₂CH₂CH₃ CH₃ 92 Cl H CH₂CH₂CO₂H CH₃ 93 NO₂ H CH₂CH₂CO₂CH₂CH₃ H 94 NO₂ H CH₂CH₂CO₂H H 95 NO₂ H CH₂CH₂CO₂CH₂CH₃ CH₃ 96 NO₂ H CH₂CH₂CO₂H CH₃ 97 NH₂ H CH₂CH₂CO₂CH₂CH₃ H 98 NH₂ H CH₂CH₂CO₂H H 99 NH₂ H CH₂CH₂CO₂CH₂CH₃ CH₃ 100 NH₂ H CH₂CH₂CO₂H CH₃ 101 NHSO₂CH₃ H CH₂CH₂CO₂CH₂CH₃ H 102 NHSO₂CH₃ H CH₂CH₂CO₂H H 103 NHSO₂CH₃ H CH₂CH₂CO₂CH₂CH₃ CH₃ 104 NHSO₂CH₃ H CH₂CH₂CO₂H CH₃ 105 OH CH₂N(CH₃)₂ CH₂CH₂CO₂CH₂CH₃ H 106 OH CH₂N(CH₃)₂ CH₂CH₂CO₂H H 107 OH CH₂N(CH₃)₂ CH₂CH₂CO₂CH₂CH₃ CH₃ 108 OH CH₂N(CH₃)₂ CH₂CH₂CO₂H CH₃ 109 OH CH₂N⁺(CH₃)₃Cl⁻ CH₂CH₂CO₂CH₂CH₃ H 110 OH CH₂N⁺(CH₃)₃Cl⁻ CH₂CH₂CO₂H H 111 OH CH₂N⁺(CH₃)₃Cl⁻ CH₂CH₂CO₂CH₂CH₃ CH₃ 112 OH CH₂N⁺(CH₃)₃Cl⁻ CH₂CH₂CO₂H CH₃ 113 OCH₃ CH₂N(CH₃)₂ CH₂CH₂CO₂CH₂CH₃ H 114 OCH₃ CH₂N(CH₃)₂ CH₂CH₂CO₂H H 115 OCH₃ CH₂N(CH₃)₂ CH₂CH₂CO₂CH₂CH₃ CH₃ 116 OCH₃ CH₂N(CH₃)₂ CH₂CH₂CO₂H CH₃ 117 OCH₃ CH₂N⁺(CH₃)₃Cl⁻ CH₂CH₂CO₂CH₂CH₃ H 1118 OCH₃ CH₂N⁺(CH₃)₃Cl⁻ CH₂CH₂CO₂H H 119 OCH₃ CH₂N⁺(CH₃)₃Cl⁻ CH₂CH₂CO₂CH₂CH₃ CH₃ 120 OCH₃ CH₂N⁺(CH₃)₃Cl⁻ CH₂CH₂CO₂H CH₃ 121 H H CH₂CH₂PO— H (OCH₂CH₃)₂ 122 H H CH₂CH₂PO—(OH)₂ H 123 H H CH₂CH₂PO— CH₃ (OCH₂CH₃)₂ 124 H H CH₂CH₂PO—(OH)₂ CH₃ 125 OH H CH₂CH₂PO— H (OCH₂CH₃)₂ 126 OH H CH₂CH₂PO—(OH)₂ H 127 OH H CH₂CH₂PO— CH₃ (OCH₂CH₃)₂ 128 OH H CH₂CH₂PO—(OH)₂ CH₃ 129 OCH₃ H CH₂CH₂PO— H (OCH₂CH₃)₂ 130 OCH₃ H CH₂CH₂PO—(OH)₂ H 131 OCH₃ H CH₂CH₂PO— CH₃ (OCH₂CH₃)₂ 132 OCH₃ H CH₂CH₂PO—(OH)₂ CH₃ 133 OCH₂C₆H₅ H CH₂CH₂PO— H (OCH₂CH₃)₂ 134 OCH₂C₆H₅ H CH₂CH₂PO—(OH)₂ H 135 OCH₂C₆H₅ H CH₂CH₂PO— CH₃ (OCH₂CH₃)₂ 136 OCH₂C₆H₅ H CH₂CH₂PO—(OH)₂ CH₃ 137 OCH₂CH₂C₆H₅ H CH₂CH₂PO— H (OCH₂CH₃)₂ 138 OCH₂CH₂C₆H₅ H CH₂CH₂PO—(OH)₂ H 139 OCH₂CH₂C₆H₅ H CH₂CH₂PO— CH₃ (OCH₂CH₃)₂ 140 OCH₂CH₂C₆H₅ H CH₂CH₂PO—(OH)₂ CH₃ 141 OCH₂CH═CH₂ H CH₂CH₂PO— H (OCH₂CH₃)₂ 142 OCH₂CH═CH₂ H CH₂CH₂PO—(OH)₂ H 143 OCH₂CH═CH₂ H CH₂CH₂PO— CH₃ (OCH₂CH₃)₂ 144 OCH₂CH═CH₂ H CH₂CH₂PO—(OH)₂ CH₃ 145 OCH₂CONH₂ H CH₂CH₂PO— H (OCH₂CH₃)₂ 146 OCH₂CONH₂ H CH₂CH₂PO—(OH)₂ H 147 OCH₂CONH₂ H CH₂CH₂PO— CH₃ (OCH₂CH₃)₂ 148 OCH₂CONH₂ H CH₂CH₂PO—(OH)₂ CH₃ 149 Cl H CH₂CH₂PO— H (OCH₂CH₃)₂ 150 Cl H CH₂CH₂PO—(OH)₂ H 151 Cl H CH₂CH₂PO— CH₃ (OCH₂CH₃)₂ 152 Cl H CH₂CH₂PO—(OH)₂ CH₃ 153 NO₂ H CH₂CH₂PO— H (OCH₂CH₃)₂ 154 NO₂ H CH₂CH₂PO—(OH)₂ H 155 NO₂ H CH₂CH₂PO— CH₃ (OCH₂CH₃)₂ 156 NO₂ H CH₂CH₂PO—(OH)₂ CH₃ 157 NH₂ H CH₂CH₂PO— H (OCH₂CH₃)₂ 158 NH₂ H CH₂CH₂PO—(OH)₂ H 159 NH₂ H CH₂CH₂PO— CH₃ (OCH₂CH₃)₂ 160 NH₂ H CH₂CH₂PO—(OH)₂ CH₃ 161 NHSO₂CH₃ H CH₂CH₂PO— H (OCH₂CH₃)₂ 162 NHSO₂CH₃ H CH₂CH₂PO—(OH)₂ H 163 NHSO₂CH₃ H CH₂CH₂PO— CH₃ (OCH₂CH₃)₂ 164 NHSO₂CH₃ H CH₂CH₂PO—(OH)₂ CH₃ 165 OH CH₂N(CH₃)₂ CH₂CH₂PO— H (OCH₂CH₃)₂ 166 OH CH₂N(CH₃)₂ CH₂CH₂PO—(OH)₂ H 167 OH CH₂N(CH₃)₂ CH₂CH₂PO— CH₃ (OCH₂CH₃)₂ 168 OH CH₂N(CH₃)₂ CH₂CH₂PO—(OH)₂ CH₃ 169 OH CH₂N⁺(CH₃)₃Cl⁻ CH₂CH₂PO— H (OCH₂CH₃)₂ 170 OH CH₂N⁺(CH₃)₃Cl⁻ CH₂CH₂PO—(OH)₂ H 171 OH CH₂N⁺(CH₃)₃Cl⁻ CH₂CH₂PO— CH₃ (OCH₂CH₃)₂ 172 OH CH₂N⁺(CH₃)₃Cl⁻ CH₂CH₂PO—(OH)₂ CH₃ 173 OCH₃ CH₂N(CH₃)₂ CH₂CH₂PO— H (OCH₂CH₃)₂ 174 OCH₃ CH₂N(CH₃)₂ CH₂CH₂PO—(OH)₂ H 175 OCH₃ CH₂N(CH₃)₂ CH₂CH₂PO— CH₃ (OCH₂CH₃)₂ 176 OCH₃ CH₂N(CH₃)₂ CH₂CH₂PO—(OH)₂ CH₃ 177 OCH₃ CH₂N⁺(CH₃)₃Cl⁻ CH₂CH₂PO— H (OCH₂CH₃)₂ 178 OCH₃ CH₂N⁺(CH₃)₃Cl⁻ CH₂CH₂PO—(OH)₂ H 179 OCH₃ CH₂N⁺(CH₃)₃Cl⁻ CH₂CH₂PO— CH₃ (OCH₂CH₃)₂ 180 OCH₃ CH₂N⁺(CH₃)₃Cl⁻ CH₂CH₂PO—(OH)₂ CH₃ 181 H H CH₂CH₂CONH— H CH(OH)CO₂H 182 H H CH₂CH₂CONH— CH₃ CH(OH)CO₂H 183 OH H CH₂CH₂CONH— H CH(OH)CO₂H 184 OH H CH₂CH₂CONH— CH₃ CH(OH)CO₂H 185 OCH₃ H CH₂CH₂CONH— H CH(OH)CO₂H 186 OCH₃ H CH₂CH₂CONH— CH₃ CH(OH)CO₂H 187 OCH₂C₆H₅ H CH₂CH₂CONH— H CH(OH)CO₂H 188 OCH₂C₆H₅ H CH₂CH₂CONH— CH₃ CH(OH)CO₂H 189 OCH₂CH₂C₆H₅ H CH₂CH₂CONH— H CH(OH)CO₂H 190 OCH₂CH₂C₆H₅ H CH₂CH₂CONH— CH₃ CH(OH)CO₂H 191 OCH₂CH═CH₂ H CH₂CH₂CONH— H CH(OH)CO₂H 192 OCH₂CH═CH₂ H CH₂CH₂CONH— CH₃ CH(OH)CO₂H 193 OCH₂CONH₂ H CH₂CH₂CONH— H CH(OH)CO₂H 194 OCH₂CONH₂ H CH₂CH₂CONH— CH₃ CH(OH)CO₂H 195 Cl H CH₂CH₂CONH— H CH(OH)CO₂H 196 Cl H CH₂CH₂CONH— CH₃ CH(OH)CO₂H 197 NO₂ H CH₂CH₂CONH— H CH(OH)CO₂H 198 NO₂ H CH₂CH₂CONH— CH₃ CH(OH)CO₂H 199 NH₂ H CH₂CH₂CONH— H CH(OH)CO₂H 200 NH₂ H CH₂CH₂CONH— CH₃ CH(OH)CO₂H 201 NHSO₂CH₃ H CH₂CH₂CONH— H CH(OH)CO₂H 202 NHSO₂CH₃ H CH₂CH₂CONH— CH₃ CH(OH)CO₂H 203 OH CH₂N(CH₃)₂ CH₂CH₂CONH— H CH(OH)CO₂H 204 OH CH₂N(CH₃)₂ CH₂CH₂CONH— CH₃ CH(OH)CO₂H 205 OH CH₂N⁺(CH₃)₃Cl⁻ CH₂CH₂CONH— H CH(OH)CO₂H 206 OH CH₂N⁺(CH₃)₃Cl⁻ CH₂CH₂CONH— CH₃ CH(OH)CO₂H 207 OCH₃ CH₂N(CH₃)₂ CH₂CH₂CONH— H CH(OH)CO₂H 208 OCH₃ CH₂N(CH₃)₂ CH₂CH₂CONH— CH₃ CH(OH)CO₂H 209 OCH₃ CH₂N⁺(CH₃)₃Cl⁻ CH₂CH₂CONH— H CH(OH)CO₂H 210 OCH₃ CH₂N⁺(CH₃)₃Cl⁻ CH₂CH₂CONH— CH₃ CH(OH)CO₂H 211 H H CH₂CH₂CONH— H C(CH₃)₂CH₂SO₃H 212 H H CH₂CH₂CONH— CH₃ C(CH₃)₂CH₂SO₃H 213 OH H CH₂CH₂CONH— H C(CH₃)₂CH₂SO₃H 214 OH H CH₂CH₂CONH— CH₃ C(CH₃)₂CH₂SO₃H 215 OCH₃ H CH₂CH₂CONH— H C(CH₃)₂CH₂SO₃H 216 OCH₃ H CH₂CH₂CONH— CH₃ C(CH₃)₂CH₂SO₃H 217 OCH₂C₆H₅ H CH₂CH₂CONH— H C(CH₃)₂CH₂SO₃H 218 OCH₂C₆H₅ H CH₂CH₂CONH— CH₃ C(CH₃)₂CH₂SO₃H 219 OCH₂CH₂C₆H₅ H CH₂CH₂CONH— H C(CH₃)₂CH₂SO₃H 220 OCH₂CH₂C₆H₅ H CH₂CH₂CONH— CH₃ C(CH₃)₂CH₂SO₃H 221 OCH₂CH═CH₂ H CH₂CH₂CONH— H C(CH₃)₂CH₂SO₃H 222 OCH₂CH═CH₂ H CH₂CH₂CONH— CH₃ C(CH₃)₂CH₂SO₃H 223 OCH₂CONH₂ H CH₂CH₂CONH— H C(CH₃)₂CH₂SO₃H 224 OCH₂CONH₂ H CH₂CH₂CONH— CH₃ C(CH₃)₂CH₂SO₃H 225 Cl H CH₂CH₂CONH— H C(CH₃)₂CH₂SO₃H 226 Cl H CH₂CH₂CONH— CH₃ C(CH₃)₂CH₂SO₃H 227 NO₂ H CH₂CH₂CONH— H C(CH₃)₂CH₂SO₃H 228 NO₂ H CH₂CH₂CONH— CH₃ C(CH₃)₂CH₂SO₃H 229 NH₂ H CH₂CH₂CONH— H C(CH₃)₂CH₂SO₃H 230 NH₂ H CH₂CH₂CONH— CH₃ C(CH₃)₂CH₂SO₃H 231 NHSO₂CH₃ H CH₂CH₂CONH— H C(CH₃)₂CH₂SO₃H 232 NHSO₂CH₃ H CH₂CH₂CONH— CH₃ C(CH₃)₂CH₂SO₃H 233 OH CH₂N(CH₃)₂ CH₂CH₂CONH— H C(CH₃)₂CH₂SO₃H 234 OH CH₂N(CH₃)₂ CH₂CH₂CONH— CH₃ C(CH₃)₂CH₂SO₃H 235 OH CH₂N⁺(CH₃)₃Cl⁻ CH₂CH₂CONH— H C(CH₃)₂CH₂SO₃H 236 OH CH₂N⁺(CH₃)₃Cl⁻ CH₂CH₂CONH— CH₃ C(CH₃)₂CH₂SO₃H 237 OCH₃ CH₂N(CH₃)₂ CH₂CH₂CONH— H C(CH₃)₂CH₂SO₃H 238 OCH₃ CH₂N(CH₃)₂ CH₂CH₂CONH— CH₃ C(CH₃)₂CH₂SO₃H 239 OCH₃ CH₂N⁺(CH₃)₃Cl⁻ CH₂CH₂CONH— H C(CH₃)₂CH₂SO₃H 240 OCH₃ CH₂N⁺(CH₃)₃Cl⁻ CH₂CH₂CONH— CH₃ C(CH₃)₂CH₂SO₃H 241 H H CH₂-tetrazole H 242 OH H CH₂-tetrazole H 243 OCH₃ H CH₂-tetrazole H 244 OCH₂C₆H₅ H CH₂-tetrazole H 245 Cl H CH₂-tetrazole H 246 CH₃ H CH₂-tetrazole H 247 H H CH₂-tetrazole CH₃ 248 OH H CH₂-tetrazole CH₃ 249 OCH₃ H CH₂-tetrazole CH₃ 250 OCH₂C₆H₅ H CH₂-tetrazole CH₃ 251 Cl H CH₂-tetrazole CH₃ 252 CH₃ H CH₂-tetrazole CH₃

TABLE IlIb

Ex. # X X¹ Z¹ R¹ 1 H H CH₂CO₂CH₂CH₃ H 2 H H CH₂CO₂H H 3 H H CH₂CO₂CH₂CH₃ CH₃ 4 H H CH₂CO₂H CH₃ 5 OH H CH₂CO₂CH₂CH₃ H 6 OH H CH₂CO₂H H 7 OH H CH₂CO₂CH₂CH₃ CH₃ 8 OH H CH₂CO₂H CH₃ 9 OCH₃ H CH₂CO₂CH₂CH₃ H 10 OCH₃ H CH₂CO₂H H 11 OCH₃ H CH₂CO₂CH₂CH₃ CH₃ 12 OCH₃ H CH₂CO₂H CH₃ 13 OCH₂C₆H₅ H CH₂CO₂CH₂CH₃ H 14 OCH₂C₆H₅ H CH₂CO₂H H 15 OCH₂C₆H₅ H CH₂CO₂CH₂CH₃ CH₃ 16 OCH₂C₆H₅ H CH₂CO₂H CH₃ 17 OCH₂CH₂C₆H₅ H CH₂CO₂CH₂CH₃ H 18 OCH₂CH₂C₆H₅ H CH₂CO₂H H 19 OCH₂CH₂C₆H₅ H CH₂CO₂CH₂CH₃ CH₃ 20 OCH₂CH₂C₆H₅ H CH₂CO₂H CH₃ 21 OCH₂CH═CH₂ H CH₂CO₂CH₂CH₃ H 22 OCH₂CH═CH₂ H CH₂CO₂H H 23 OCH₂CH═CH₂ H CH₂CO₂CH₂CH₃ CH₃ 24 OCH₂CH═CH₂ H CH₂CO₂H CH₃ 25 OCH₂CONH₂ H CH₂CO₂CH₂CH₃ H 26 OCH₂CONH₂ H CH₂CO₂H H 27 OCH₂CONH₂ H CH₂CO₂CH₂CH₃ CH₃ 28 OCH₂CONH₂ H CH₂CO₂H CH₃ 29 Cl H CH₂CO₂CH₂CH₃ H 30 Cl H CH₂CO₂H H 31 Cl H CH₂CO₂CH₂CH₃ CH₃ 32 Cl H CH₂CO₂H CH₃ 33 NO₂ H CH₂CO₂CH₂CH₃ H 34 NO₂ H CH₂CO₂H H 35 NO₂ H CH₂CO₂CH₂CH₃ CH₃ 36 NO₂ H CH₂CO₂H CH₃ 37 H H CH₂CH₂CO₂CH₂CH₃ H 38 H H CH₂CH₂CO₂H H 39 H H CH₂CH₂CO₂CH₂CH₃ CH₃ 40 H H CH₂CH₂CO₂H CH₃ 41 OH H CH₂CH₂CO₂CH₂CH₃ H 42 OH H CH₂CH₂CO₂H H 43 OH H CH₂CH₂CO₂CH₂CH₃ CH₃ 44 OH H CH₂CH₂CO₂H CH₃ 45 OCH₃ H CH₂CH₂CO₂CH₂CH₃ H 46 OCH₃ H CH₂CH₂CO₂H H 47 OCH₃ H CH₂CH₂CO₂CH₂CH₃ CH₃ 48 OCH₃ H CH₂CH₂CO₂H CH₃ 49 OCH₂C₆H₅ H CH₂CH₂CO₂CH₂CH₃ H 50 OCH₂C₆H₅ H CH₂CH₂CO₂H H 51 OCH₂C₆H₅ H CH₂CH₂CO₂CH₂CH₃ CH₃ 52 OCH₂C₆H₅ H CH₂CH₂CO₂H CH₃ 53 OCH₂CH₂C₆H₅ H CH₂CH₂CO₂CH₂CH₃ H 54 OCH₂CH₂C₆H₅ H CH₂CH₂CO₂H H 55 OCH₂CH₂C₆H₅ H CH₂CH₂CO₂CH₂CH₃ CH₃ 56 OCH₂CH₂C₆H₅ H CH₂CH₂CO₂H CH₃ 57 OCH₂CH═CH₂ H CH₂CH₂CO₂CH₂CH₃ H 58 OCH₂CH═CH₂ H CH₂CH₂CO₂H H 59 OCH₂CH═CH₂ H CH₂CH₂CO₂CH₂CH₃ CH₃ 60 OCH₂CH═CH₂ H CH₂CH₂CO₂H CH₃ 61 OCH₂CONH₂ H CH₂CH₂CO₂CH₂CH₃ H 62 OCH₂CONH₂ H CH₂CH₂CO₂H H 63 OCH₂CONH₂ H CH₂CH₂CO₂CH₂CH₃ CH₃ 64 OCH₂CONH₂ H CH₂CH₂CO₂H CH₃ 65 Cl H CH₂CH₂CO₂CH₂CH₃ H 66 Cl H CH₂CH₂CO₂H H 67 Cl H CH₂CH₂CO₂CH₂CH₃ CH₃ 68 Cl H CH₂CH₂CO₂H CH₃ 69 NO₂ H CH₂CH₂CO₂CH₂CH₃ H 70 NO₂ H CH₂CH₂CO₂H H 71 NO₂ H CH₂CH₂CO₂CH₂CH₃ CH₃ 72 NO₂ H CH₂CH₂CO₂H CH₃ 73 H H CH₂CH₂PO—(OCH₂CH₃)₂ H 74 H H CH₂CH₂PO—(OH)₂ H 75 H H CH₂CH₂PO—(OCH₂CH₃)₂ CH₃ 76 H H CH₂CH₂PO—(OH)₂ CH₃ 77 OH H CH₂CH₂PO—(OCH₂CH₃)₂ H 78 OH H CH₂CH₂PO—(OH)₂ H 79 OH H CH₂CH₂PO—(OCH₂CH₃)₂ CH₃ 80 OH H CH₂CH₂PO—(OH)₂ CH₃ 81 OCH₃ H CH₂CH₂PO—(OCH₂CH₃)₂ H 82 OCH₃ H CH₂CH₂PO—(OH)₂ H 83 OCH₃ H CH₂CH₂PO—(OCH₂CH₃)₂ CH₃ 84 OCH₃ H CH₂CH₂PO—(OH)₂ CH₃ 85 OCH₂C₆H₅ H CH₂CH₂PO—(OCH₂CH₃)₂ H 86 OCH₂C₆H₅ H CH₂CH₂PO—(OH)₂ H 87 OCH₂C₆H₅ H CH₂CH₂PO—(OCH₂CH₃)₂ CH₃ 88 OCH₂C₆H₅ H CH₂CH₂PO—(OH)₂ CH₃ 89 OCH₂CH₂C₆H₅ H CH₂CH₂PO—(OCH₂CH₃)₂ H 90 OCH₂CH₂C₆H₅ H CH₂CH₂PO—(OH)₂ H 91 OCH₂CH₂C₆H₅ H CH₂CH₂PO—(OCH₂CH₃)₂ CH₃ 92 OCH₂CH₂C₆H₅ H CH₂CH₂PO—(OH)₂ CH₃ 93 OCH₂CH═CH₂ H CH₂CH₂PO—(OCH₂CH₃)₂ H 94 OCH₂CH═CH₂ H CH₂CH₂PO—(OH)₂ H 95 OCH₂CH═CH₂ H CH₂CH₂PO—(OCH₂CH₃)₂ CH₃ 96 OCH₂CH═CH₂ H CH₂CH₂PO—(OH)₂ CH₃ 97 OCH₂CONH₂ H CH₂CH₂PO—(OCH₂CH₃)₂ H 98 OCH₂CONH₂ H CH₂CH₂PO—(OH)₂ H 99 OCH₂CONH₂ H CH₂CH₂PO—(OCH₂CH₃)₂ CH₃ 100 OCH₂CONH₂ H CH₂CH₂PO—(OH)₂ CH₃ 101 Cl H CH₂CH₂PO—(OCH₂CH₃)₂ H 102 Cl H CH₂CH₂PO—(OH)₂ H 103 Cl H CH₂CH₂PO—(OCH₂CH₃)₂ CH₃ 104 Cl H CH₂CH₂PO—(OH)₂ CH₃ 105 NO₂ H CH₂CH₂PO—(OCH₂CH₃)₂ H 106 NO₂ H CH₂CH₂PO—(OH)₂ H 107 NO₂ H CH₂CH₂PO—(OCH₂CH₃)₂ CH₃ 108 NO₂ H CH₂CH₂PO—(OH)₂ CH₃ 109 H H CH₂CH₂CONH— H CH(OH)CO₂H 110 H H CH₂CH₂CONH— CH₃ CH(OH)CO₂H 111 OH H CH₂CH₂CONH— H CH(OH)CO₂H 112 OH H CH₂CH₂CONH— CH₃ CH(OH)CO₂H 113 OCH₃ H CH₂CH₂CONH— H CH(OH)CO₂H 114 OCH₃ H CH₂CH₂CONH— CH₃ CH(OH)CO₂H 115 OCH₂C₆H₅ H CH₂CH₂CONH— H CH(OH)CO₂H 116 OCH₂C₆H₅ H CH₂CH₂CONH— CH₃ CH(OH)CO₂H 117 OCH₂CH₂C₆H₅ H CH₂CH₂CONH— H CH(OH)CO₂H 118 OCH₂CH₂C₆H₅ H CH₂CH₂CONH— CH₃ CH(OH)CO₂H 119 OCH₂CH═CH₂ H CH₂CH₂CONH— H CH(OH)CO₂H 120 OCH₂CH═CH₂ H CH₂CH₂CONH— CH₃ CH(OH)CO₂H 121 OCH₂CONH₂ H CH₂CH₂CONH— H CH(OH)CO₂H 122 OCH₂CONH₂ H CH₂CH₂CONH— CH₃ CH(OH)CO₂H 123 Cl H CH₂CH₂CONH— H CH(OH)CO₂H 124 Cl H CH₂CH₂CONH— CH₃ CH(OH)CO₂H 125 NO₂ H CH₂CH₂CONH— H CH(OH)CO₂H 126 NO₂ H CH₂CH₂CONH— CH₃ CH(OH)CO₂H 127 H H CH₂CH₂CONH— H C(CH₃)₂CH₂SO₃H 128 H H CH₂CH₂CONH— CH₃ C(CH₃)₂CH₂SO₃H 129 OH H CH₂CH₂CONH— H C(CH₃)₂CH₂SO₃H 130 OH H CH₂CH₂CONH— CH₃ C(CH₃)₂CH₂SO₃H 131 OCH₃ H CH₂CH₂CONH— H C(CH₃)₂CH₂SO₃H 132 OCH₃ H CH₂CH₂CONH— CH₃ C(CH₃)₂CH₂SO₃H 133 OCH₂C₆H₅ H CH₂CH₂CONH— H C(CH₃)₂CH₂SO₃H 134 OCH₂C₆H₅ H CH₂CH₂CONH— CH₃ C(CH₃)₂CH₂SO₃H 135 OCH₂CH₂C₆H₅ H CH₂CH₂CONH— H C(CH₃)₂CH₂SO₃H 136 OCH₂CH₂C₆H₅ H CH₂CH₂CONH— CH₃ C(CH₃)₂CH₂SO₃H 137 OCH₂CH═CH₂ H CH₂CH₂CONH— H C(CH₃)₂CH₂SO₃H 138 OCH₂CH═CH₂ H CH₂CH₂CONH— CH₃ C(CH₃)₂CH₂SO₃H 139 OCH₂CONH₂ H CH₂CH₂CONH— H C(CH₃)₂CH₂SO₃H 140 OCH₂CONH₂ H CH₂CH₂CONH— CH₃ C(CH₃)₂CH₂SO₃H 141 Cl H CH₂CH₂CONH— H C(CH₃)₂CH₂SO₃H 142 Cl H CH₂CH₂CONH— CH₃ C(CH₃)₂CH₂SO₃H 143 NO₂ H CH₂CH₂CONH— H C(CH₃)₂CH₂SO₃H 144 NO₂ H CH₂CH₂CONH— CH₃ C(CH₃)₂CH₂SO₃H

TABLE IVa

Ex. # X Z R¹ 1 OCH₂CO₂CH₂CH₃ H H 2 OCH₂CO₂H H H 3 OCH₂CO₂CH₂CH₃ H CH₃ 4 OCH₂CO₂H H CH₃ 5 OCH₂CH₂CO₂CH₂CH₃ H H 6 OCH₂CH₂CO₂H H H 7 OCH₂CH₂CO₂CH₂CH₃ H CH₃ 8 OCH₂CH₂CO₂H H CH₃ 9 OCH₂CH₂PO(OCH₂CH₃)₂ H H 10 OCH₂CH₂PO(OH)₂ H H 11 OCH₂CH₂PO(OCH₂CH₃)₂ H CH₃ 12 OCH₂CH₂PO(OH)₂ H CH₃ 13 OCH₂CH═CHCO₂CH₂CH₃ H H 14 OCH₂CH═CHCO₂H H H 15 OCH₂CH═CHCO₂CH₂CH₃ H CH₃ 16 OCH₂CH═CHCO₂H H CH₃ 17 OCH₂C₆H₄CO₂CH₂CH₃(2, 3 or 4) H H 18 OCH₂C₆H₄CO₂H(2, 3 or 4) H H 19 OCH₂C₆H₄CO₂CH₂CH₃(2, 3 or 4) H CH₃ 20 OCH₂C₆H₄CO₂H(2, 3 or 4) H CH₃ 21 OCH₂C₆H₄CH₂CO₂CH₂CH₃(2, 3 or 4) H H 22 OCH₂C₆H₄CH₂CO₂H(2, 3 or 4) H H 23 OCH₂C₆H₄CH₂CO₂CH₂CH₃(2, 3 or 4) H CH₃ 24 OCH₂C₆H₄CH₂CO₂H(2, 3 or 4) H CH₃ 25 OCH₂CO₂CH₂CH₃ OH H 26 OCH₂CO₂H OH H 27 OCH₂CO₂CH₂CH₃ OH CH₃ 28 OCH₂CO₂H OH CH₃ 29 OCH₂CH₂CO₂CH₂CH₃ OH H 30 OCH₂CH₂CO₂H OH H 31 OCH₂CH₂CO₂CH₂CH₃ OH CH₃ 32 OCH₂CH₂CO₂H OH CH₃ 33 OCH₂CH₂PO(OCH₂CH₃)₂ OH H 34 OCH₂CH₂PO(OH)₂ OH H 35 OCH₂CH₂PO(OCH₂CH₃)₂ OH CH₃ 36 OCH₂CH₂PO(OH)₂ OH CH₃ 37 OCH₂CH═CHCO₂CH₂CH₃ OH H 38 OCH₂CH═CHCO₂H OH H 39 OCH₂CH═CHCO₂CH₂CH₃ OH CH₃ 40 OCH₂CH═CHCO₂H OH CH₃ 41 OCH₂C₆H₄CO₂CH₂CH₃(2, 3 or 4) OH H 42 OCH₂C₆H₄CO₂H(2, 3 or 4) OH H 43 OCH₂C₆H₄CO₂CH₂CH₃(2, 3 or 4) OH CH₃ 44 OCH₂C₆H₄CO₂H(2, 3 or 4) OH CH₃ 45 OCH₂C₆H₄CH₂CO₂CH₂CH₃(2, 3 or 4) OH H 46 OCH₂C₆H₄CH₂CO₂H(2, 3 or 4) OH H 47 OCH₂C₆H₄CH₂CO₂CH₂CH₃(2, 3 or 4) OH CH₃ 48 OCH₂C₆H₄CH₂CO₂H(2, 3 or 4) OH CH₃ 49 OCH₂CO₂CH₂CH₃ OCH₃ H 50 OCH₂CO₂H OCH₃ H 51 OCH₂CO₂CH₂CH₃ OCH₃ CH₃ 52 OCH₂CO₂H OCH₃ CH₃ 53 OCH₂CH₂CO₂CH₂CH₃ OCH₃ H 54 OCH₂CH₂CO₂H OCH₃ H 55 OCH₂CH₂CO₂CH₂CH₃ OCH₃ CH₃ 56 OCH₂CH₂CO₂H OCH₃ CH₃ 57 OCH₂CH₂PO(OCH₂CH₃)₂ OCH₃ H 58 OCH₂CH₂PO(OH)₂ OCH₃ H 59 OCH₂CH₂PO(OCH₂CH₃)₂ OCH₃ CH₃ 60 OCH₂CH₂PO(OH)₂ OCH₃ CH₃ 61 OCH₂CH═CHCO₂CH₂CH₃ OCH₃ H 62 OCH₂CH═CHCO₂H OCH₃ H 63 OCH₂CH═CHCO₂CH₂CH₃ OCH₃ CH₃ 64 OCH₂CH═CHCO₂H OCH₃ CH₃ 65 OCH₂C₆H₄CO₂CH₂CH₃(2, 3 or 4) OCH₃ H 66 OCH₂C₆H₄CO₂H(2, 3 or 4) OCH₃ H 67 OCH₂C₆H₄CO₂CH₂CH₃(2, 3 or 4) OCH₃ CH₃ 68 OCH₂C₆H₄CO₂H(2, 3 or 4) OCH₃ CH₃ 69 OCH₂C₆H₄CH₂CO₂CH₂CH₃(2, 3 or 4) OCH₃ H 70 OCH₂C₆H₄CH₂CO₂H(2, 3 or 4) OCH₃ H 71 OCH₂C₆H₄CH₂CO₂CH₂CH₃(2, 3 or 4) OCH₃ CH₃ 72 OCH₂C₆H₄CH₂CO₂H(2, 3 or 4) OCH₃ CH₃ 73 OCH₂CO₂CH₂CH₃ OCH₂CH═CH₂ H 74 OCH₂CO₂H OCH₂CH═CH₂ H 75 OCH₂CO₂CH₂CH₃ OCH₂CH═CH₂ CH₃ 76 OCH₂CO₂H OCH₂CH═CH₂ CH₃ 77 OCH₂CH₂CO₂CH₂CH₃ OCH₂CH═CH₂ H 78 OCH₂CH₂CO₂H OCH₂CH═CH₂ H 79 OCH₂CH₂CO₂CH₂CH₃ OCH₂CH═CH₂ CH₃ 80 OCH₂CH₂CO₂H OCH₂CH═CH₂ CH₃ 81 OCH₂CH₂PO(OCH₂CH₃)₂ OCH₂CH═CH₂ H 82 OCH₂CH₂PO(OH)₂ OCH₂CH═CH₂ H 83 OCH₂CH₂PO(OCH₂CH₃)₂ OCH₂CH═CH₂ CH₃ 84 OCH₂CH₂PO(OH)₂ OCH₂CH═CH₂ CH₃ 85 OCH₂CH═CHCO₂CH₂CH₃ OCH₂CH═CH₂ H 86 OCH₂CH═CHCO₂H OCH₂CH═CH₂ H 87 OCH₂CH═CHCO₂CH₂CH₃ OCH₂CH═CH₂ CH₃ 88 OCH₂CH═CHCO₂H OCH₂CH═CH₂ CH₃ 89 OCH₂C₆H₄CO₂CH₂CH₃(2, 3 or 4) OCH₂CH═CH₂ H 90 OCH₂C₆H₄CO₂H(2, 3 or 4) OCH₂CH═CH₂ H 91 OCH₂C₆H₄CO₂CH₂CH₃(2, 3 or 4) OCH₂CH═CH₂ CH₃ 92 OCH₂C₆H₄CO₂H(2, 3 or 4) OCH₂CH═CH₂ CH₃ 93 OCH₂C₆H₄CH₂CO₂CH₂CH₃(2, 3 or 4) OCH₂CH═CH₂ H 94 OCH₂C₆H₄CH₂CO₂H(2, 3 or 4) OCH₂CH═CH₂ H 95 OCH₂C₆H₄CH₂CO₂CH₂CH₃(2, 3 or 4) OCH₂CH═CH₂ CH₃ 96 OCH₂C₆H₄CH₂CO₂H(2, 3 or 4) OCH₂CH═CH₂ CH₃ 97 OCH₂CO₂CH₂CH₃ OCH₂C₆CH₅ H 98 OCH₂CO₂H OCH₂C₆CH₅ H 99 OCH₂CO₂CH₂CH₃ OCH₂C₆CH₅ CH₃ 100 OCH₂CO₂H OCH₂C₆CH₅ CH₃ 101 OCH₂CH₂CO₂CH₂CH₃ OCH₂C₆CH₅ H 102 OCH₂CH₂CO₂H OCH₂C₆CH₅ H 103 OCH₂CH₂CO₂CH₂CH₃ OCH₂C₆CH₅ CH₃ 104 OCH₂CH₂CO₂H OCH₂C₆CH₅ CH₃ 105 OCH₂CH₂PO(OCH₂CH₃)₂ OCH₂C₆CH₅ H 106 OCH₂CH₂PO(OH)₂ OCH₂C₆CH₅ H 107 OCH₂CH₂PO(OCH₂CH₃)₂ OCH₂C₆CH₅ CH₃ 108 OCH₂CH₂PO(OH)₂ OCH₂C₆CH₅ CH₃ 109 OCH₂CH═CHCO₂CH₂CH₃ OCH₂C₆CH₅ H 110 OCH₂CH═CHCO₂H OCH₂C₆CH₅ H 111 OCH₂CH═CHCO₂CH₂CH₃ OCH₂C₆CH₅ CH₃ 112 OCH₂CH═CHCO₂H OCH₂C₆CH₅ CH₃ 113 OCH₂CO₂CH₂CH₃ OCH₂CONH₂ H 114 OCH₂CO₂H OCH₂CONH₂ H 115 OCH₂CO₂CH₂CH₃ OCH₂CONH₂ CH₃ 116 OCH₂CO₂H OCH₂CONH₂ CH₃ 117 OCH₂CH₂CO₂CH₂CH₃ OCH₂CONH₂ H 118 OCH₂CH₂CO₂H OCH₂CONH₂ H 119 OCH₂CH₂CO₂CH₂CH₃ OCH₂CONH₂ CH₃ 120 OCH₂CH₂CO₂H OCH₂CONH₂ CH₃ 121 OCH₂CH₂PO(OCH₂CH₃)₂ OCH₂CONH₂ H 122 OCH₂CH₂PO(OH)₂ OCH₂CONH₂ H 123 OCH₂CH₂PO(OCH₂CH₃)₂ OCH₂CONH₂ CH₃ 124 OCH₂CH₂PO(OH)₂ OCH₂CONH₂ CH₃ 125 OCH₂CH═CHCO₂CH₂CH₃ OCH₂CONH₂ H 126 OCH₂CH═CHCO₂H OCH₂CONH₂ H 127 OCH₂CH═CHCO₂CH₂CH₃ OCH₂CONH₂ CH₃ 128 OCH₂CH═CHCO₂H OCH₂CONH₂ CH₃ 129 OCH₂-tetrazole H H 130 OCH₂-tetrazole H CH₃ 131 OCH₂-tetrazole OH H 132 OCH₂-tetrazole OH CH₃ 133 OCH₂-tetrazole OCH₃ H 134 OCH₂-tetrazole OCH₃ CH₃ 135 OCH₂-tetrazole OCH₂CH═CH₂ H 136 OCH₂-tetrazole OCH₂CH═CH₂ CH₃ 137 OCH₂-tetrazole OCH₂C₆CH₅ H 138 OCH₂-tetrazole OCH₂C₆CH₅ CH₃ 139 CH₂-tetrazole H H 140 CH₂-tetrazole H CH₃ 141 CH₂-tetrazole OH H 142 CH₂-tetrazole OH CH₃ 143 CH₂-tetrazole OCH₃ H 144 CH₂-tetrazole OCH₃ CH₃ 145 CH₂-tetrazole OCH₂CH═CH₂ H 146 CH₂-tetrazole OCH₂CH═CH₂ CH₃ 147 CH₂-tetrazole OCH₂C₆CH₅ H 148 CH₂-tetrazole OCH₂C₆CH₅ CH₃ 149 CH₂CH₂-tetrazole H H 150 CH₂CH₂-tetrazole H CH₃ 151 CH₂CH₂-tetrazole OH H 152 CH₂CH₂-tetrazole OH CH₃ 153 CH₂CH₂-tetrazole OCH₃ H 154 CH₂CH₂-tetrazole OCH₃ CH₃ 155 CH₂CH₂-tetrazole OCH₂CH═CH₂ H 156 CH₂CH₂-tetrazole OCH₂CH═CH₂ CH₃ 157 CH₂CH₂-tetrazole OCH₂C₆CH₅ H 158 CH₂CH₂-tetrazole OCH₂C₆CH₅ CH₃ 159 OCH₂CH₂—N⁺(CH₃)₃X⁻ H H 160 OCH₂CH₂—N⁺(CH₃)₃X⁻ H CH₃ 161 OCH₂CH₂—N⁺(CH₃)₃X⁻ OCH₃ H 162 OCH₂CH₂—N⁺(CH₃)₃X⁻ OCH₃ CH₃ 163 OCH₂CH₂—N⁺(CH₃)₃X⁻ OCH₂CH═CH₂ H 164 OCH₂CH₂—N⁺(CH₃)₃X⁻ OCH₂CH═CH₂ CH₃ 165 OCH₂CH₂—N⁺(CH₃)₃X⁻ OCH₂C₆CH₅ H 166 OCH₂CH₂—N⁺(CH₃)₃X⁻ OCH₂C₆CH₅ CH₃

TABLE IVb

Ex. # X¹ Z R¹ 1 OCH₂CO₂CH₂CH₃ H H 2 OCH₂CO₂H H H 3 OCH₂CO₂CH₂CH₃ H CH₃ 4 OCH₂CO₂H H CH₃ 5 OCH₂CH₂CO₂CH₂CH₃ H H 6 OCH₂CH₂CO₂H H H 7 OCH₂CH₂CO₂CH₂CH₃ H CH₃ 8 OCH₂CH₂CO₂H H CH₃ 9 OCH₂CH₂PO(OCH₂CH₃)₂ H H 10 OCH₂CH₂PO(OH)₂ H H 11 OCH₂CH₂PO(OCH₂CH₃)₂ H CH₃ 12 OCH₂CH₂PO(OH)₂ H CH₃ 13 OCH₂CH═CHCO₂CH₂CH₃ H H 14 OCH₂CH═CHCO₂H H H 15 OCH₂CH═CHCO₂CH₂CH₃ H CH₃ 16 OCH₂CH═CHCO₂H H CH₃ 17 OCH₂C₆H₄CO₂CH₂CH₃(2, 3 or 4) H H 18 OCH₂C₆H₄CO₂H(2, 3 or 4) H H 19 OCH₂C₆H₄CO₂CH₂CH₃(2, 3 or 4) H CH₃ 20 OCH₂C₆H₄CO₂H(2, 3 or 4) H CH₃ 21 OCH₂C₆H₄CH₂CO₂CH₂CH₃(2, 3 or 4) H H 22 OCH₂C₆H₄CH₂CO₂H(2, 3 or 4) H H 23 OCH₂C₆H₄CH₂CO₂CH₂CH₃(2, 3 or 4) H CH₃ 24 OCH₂C₆H₄CH₂CO₂H(2, 3 or 4) H CH₃ 25 OCH₂CO₂CH₂CH₃ OH H 26 OCH₂CO₂H OH H 27 OCH₂CO₂CH₂CH₃ OH CH₃ 28 OCH₂CO₂H OH CH₃ 29 OCH₂CH₂CO₂CH₂CH₃ OH H 30 OCH₂CH₂CO₂H OH H 31 OCH₂CH₂CO₂CH₂CH₃ OH CH₃ 32 OCH₂CH₂CO₂H OH CH₃ 33 OCH₂CH₂PO(OCH₂CH₃)₂ OH H 34 OCH₂CH₂PO(OH)₂ OH H 35 OCH₂CH₂PO(OCH₂CH₃)₂ OH CH₃ 36 OCH₂CH₂PO(OH)₂ OH CH₃ 37 OCH₂CH═CHCO₂CH₂CH₃ OH H 38 OCH₂CH═CHCO₂H OH H 39 OCH₂CH═CHCO₂CH₂CH₃ OH CH₃ 40 OCH₂CH═CHCO₂H OH CH₃ 41 OCH₂C₆H₄CO₂CH₂CH₃(2, 3 or 4) OH H 42 OCH₂C₆H₄CO₂H(2, 3 or 4) OH H 43 OCH₂C₆H₄CO₂CH₂CH₃(2, 3 or 4) OH CH₃ 44 OCH₂C₆H₄CO₂H(2, 3 or 4) OH CH₃ 45 OCH₂C₆H₄CH₂CO₂CH₂CH₃(2, 3 or 4) OH H 46 OCH₂C₆H₄CH₂CO₂H(2, 3 or 4) OH H 47 OCH₂C₆H₄CH₂CO₂CH₂CH₃(2, 3 or 4) OH CH₃ 48 OCH₂C₆H₄CH₂CO₂H(2, 3 or 4) OH CH₃ 49 OCH₂CO₂CH₂CH₃ OCH₃ H 50 OCH₂CO₂H OCH₃ H 51 OCH₂CO₂CH₂CH₃ OCH₃ CH₃ 52 OCH₂CO₂H OCH₃ CH₃ 53 OCH₂CH₂CO₂CH₂CH₃ OCH₃ H 54 OCH₂CH₂CO₂H OCH₃ H 55 OCH₂CH₂CO₂CH₂CH₃ OCH₃ CH₃ 56 OCH₂CH₂CO₂H OCH₃ CH₃ 57 OCH₂CH₂PO(OCH₂CH₃)₂ OCH₃ H 58 OCH₂CH₂PO(OH)₂ OCH₃ H 59 OCH₂CH₂PO(OCH₂CH₃)₂ OCH₃ CH₃ 60 OCH₂CH₂PO(OH)₂ OCH₃ CH₃ 61 OCH₂CH═CHCO₂CH₂CH₃ OCH₃ H 62 OCH₂CH═CHCO₂H OCH₃ H 63 OCH₂CH═CHCO₂CH₂CH₃ OCH₃ CH₃ 64 OCH₂CH═CHCO₂H OCH₃ CH₃ 65 OCH₂C₆H₄CO₂CH₂CH₃(2, 3 or 4) OCH₃ H 66 OCH₂C₆H₄CO₂H(2, 3 or 4) OCH₃ H 67 OCH₂C₆H₄CO₂CH₂CH₃(2, 3 or 4) OCH₃ CH₃ 68 OCH₂C₆H₄CO₂H(2, 3 or 4) OCH₃ CH₃ 69 OCH₂C₆H₄CH₂CO₂CH₂CH₃(2, 3 or 4) OCH₃ H 70 OCH₂C₆H₄CH₂CO₂H(2, 3 or 4) OCH₃ H 71 OCH₂C₆H₄CH₂CO₂CH₂CH₃(2, 3 or 4) OCH₃ CH₃ 72 OCH₂C₆H₄CH₂CO₂H(2, 3 or 4) OCH₃ CH₃ 73 OCH₂CO₂CH₂CH₃ OCH₂CH═CH₂ H 74 OCH₂CO₂H OCH₂CH═CH₂ H 75 OCH₂CO₂CH₂CH₃ OCH₂CH═CH₂ CH₃ 76 OCH₂CO₂H OCH₂CH═CH₂ CH₃ 77 OCH₂CH₂CO₂CH₂CH₃ OCH₂CH═CH₂ H 78 OCH₂CH₂CO₂H OCH₂CH═CH₂ H 79 OCH₂CH₂CO₂CH₂CH₃ OCH₂CH═CH₂ CH₃ 80 OCH₂CH₂CO₂H OCH₂CH═CH₂ CH₃ 81 OCH₂CH₂PO(OCH₂CH₃)₂ OCH₂CH═CH₂ H 82 OCH₂CH₂PO(OH)₂ OCH₂CH═CH₂ H 83 OCH₂CH₂PO(OCH₂CH₃)₂ OCH₂CH═CH₂ CH₃ 84 OCH₂CH₂PO(OH)₂ OCH₂CH═CH₂ CH₃ 85 OCH₂CH═CHCO₂CH₂CH₃ OCH₂CH═CH₂ H 86 OCH₂CH═CHCO₂H OCH₂CH═CH₂ H 87 OCH₂CH═CHCO₂CH₂CH₃ OCH₂CH═CH₂ CH₃ 88 OCH₂CH═CHCO₂H OCH₂CH═CH₂ CH₃ 89 OCH₂C₆H₄CO₂CH₂CH₃(2, 3 or 4) OCH₂CH═CH₂ H 90 OCH₂C₆H₄CO₂H(2, 3 or 4) OCH₂CH═CH₂ H 91 OCH₂C₆H₄CO₂CH₂CH₃(2, 3 or 4) OCH₂CH═CH₂ CH₃ 92 OCH₂C₆H₄CO₂H(2, 3 or 4) OCH₂CH═CH₂ CH₃ 93 OCH₂C₆H₄CH₂CO₂CH₂CH₃(2, 3 or 4) OCH₂CH═CH₂ H 94 OCH₂C₆H₄CH₂CO₂H(2, 3 or 4) OCH₂CH═CH₂ H 95 OCH₂C₆H₄CH₂CO₂CH₂CH₃(2, 3 or 4) OCH₂CH═CH₂ CH₃ 96 OCH₂C₆H₄CH₂CO₂H(2, 3 or 4) OCH₂CH═CH₂ CH₃ 97 OCH₂CO₂CH₂CH₃ OCH₂C₆CH₅ H 98 OCH₂CO₂H OCH₂C₆CH₅ H 99 OCH₂CO₂CH₂CH₃ OCH₂C₆CH₅ CH₃ 100 OCH₂CO₂H OCH₂C₆CH₅ CH₃ 101 OCH₂CH₂CO₂CH₂CH₃ OCH₂C₆CH₅ H 102 OCH₂CH₂CO₂H OCH₂C₆CH₅ H 103 OCH₂CH₂CO₂CH₂CH₃ OCH₂C₆CH₅ CH₃ 104 OCH₂CH₂CO₂H OCH₂C₆CH₅ CH₃ 105 OCH₂CH₂PO(OCH₂CH₃)₂ OCH₂C₆CH₅ H 106 OCH₂CH₂PO(OH)₂ OCH₂C₆CH₅ H 107 OCH₂CH₂PO(OCH₂CH₃)₂ OCH₂C₆CH₅ CH₃ 108 OCH₂CH₂PO(OH)₂ OCH₂C₆CH₅ CH₃ 109 OCH₂CH═CHCO₂CH₂CH₃ OCH₂C₆CH₅ H 110 OCH₂CH═CHCO₂H OCH₂C₆CH₅ H 111 OCH₂CH═CHCO₂CH₂CH₃ OCH₂C₆CH₅ CH₃ 112 OCH₂CH═CHCO₂H OCH₂C₆CH₅ CH₃ 113 OCH₂CO₂CH₂CH₃ OCH₂CONH₂ H 114 OCH₂CO₂H OCH₂CONH₂ H 115 OCH₂CO₂CH₂CH₃ OCH₂CONH₂ CH₃ 116 OCH₂CO₂H OCH₂CONH₂ CH₃ 117 OCH₂CH₂CO₂CH₂CH₃ OCH₂CONH₂ H 118 OCH₂CH₂CO₂H OCH₂CONH₂ H 119 OCH₂CH₂CO₂CH₂CH₃ OCH₂CONH₂ CH₃ 120 OCH₂CH₂CO₂H OCH₂CONH₂ CH₃ 121 OCH₂CH₂PO(OCH₂CH₃)₂ OCH₂CONH₂ H 122 OCH₂CH₂PO(OH)₂ OCH₂CONH₂ H 123 OCH₂CH₂PO(OCH₂CH₃)₂ OCH₂CONH₂ CH₃ 124 OCH₂CH₂PO(OH)₂ OCH₂CONH₂ CH₃ 125 OCH₂CH═CHCO₂CH₂CH₃ OCH₂CONH₂ H 126 OCH₂CH═CHCO₂H OCH₂CONH₂ H 127 OCH₂CH═CHCO₂CH₂CH₃ OCH₂CONH₂ CH₃ 128 OCH₂CH═CHCO₂H OCH₂CONH₂ CH₃ 129 OCH₂-tetrazole H H 130 OCH₂-tetrazole H CH₃ 131 OCH₂-tetrazole OH H 132 OCH₂-tetrazole OH CH₃ 133 OCH₂-tetrazole OCH₃ H 134 OCH₂-tetrazole OCH₃ CH₃ 135 OCH₂-tetrazole OCH₂CH═CH₂ H 136 OCH₂-tetrazole OCH₂CH═CH₂ CH₃ 137 OCH₂-tetrazole OCH₂C₆CH₅ H 138 OCH₂-tetrazole OCH₂C₆CH₅ CH₃ 139 CH₂-tetrazole H H 140 CH₂-tetrazole H CH₃ 141 CH₂-tetrazole OH H 142 CH₂-tetrazole OH CH₃ 143 CH₂-tetrazole OCH₃ H 144 CH₂-tetrazole OCH₃ CH₃ 145 CH₂-tetrazole OCH₂CH═CH₂ H 146 CH₂-tetrazole OCH₂CH═CH₂ CH₃ 147 CH₂-tetrazole OCH₂C₆CH₅ H 148 CH₂-tetrazole OCH₂C₆CH₅ CH₃ 149 CH₂CH₂-tetrazole H H 140 CH₂CH₂-tetrazole H CH₃ 151 CH₂CH₂-tetrazole OH H 152 CH₂CH₂-tetrazole OH CH₃ 153 CH₂CH₂-tetrazole OCH₃ H 154 CH₂CH₂-tetrazole OCH₃ CH₃ 155 CH₂CH₂-tetrazole OCH₂CH═CH₂ H 156 CH₂CH₂-tetrazole OCH₂CH═CH₂ CH₃ 157 CH₂CH₂-tetrazole OCH₂C₆CH₅ H 158 CH₂CH₂-tetrazole OCH₂C₆CH₅ CH₃ 159 OCH₂CH₂—N⁺(CH₃)₃X⁻ H H 160 OCH₂CH₂—N⁺(CH₃)₃X⁻ H CH₃ 161 OCH₂CH₂—N⁺(CH₃)₃X⁻ OCH₃ H 162 OCH₂CH₂—N⁺(CH₃)₃X⁻ OCH₃ CH₃ 163 OCH₂CH₂—N⁺(CH₃)₃X⁻ OCH₂CH═CH₂ H 164 OCH₂CH₂—N⁺(CH₃)₃X⁻ OCH₂CH═CH₂ CH₃ 165 OCH₂CH₂—N⁺(CH₃)₃X⁻ OCH₂C₆CH₅ H 166 OCH₂CH₂—N⁺(CH₃)₃X⁻ OCH₂C₆CH₅ CH₃

TABLE IVc

Ex. # X Z R¹ 1 OCH₂CO₂H N(CH₃)₂ H 2 OCH₂CO₂CH₂CH₃ N(CH₃)₂ CH₃ 3 OCH₂CO₂H N(CH₃)₂ CH₃ 4 OCH₂CH₂CO₂CH₂CH₃ N(CH₃)₂ H 5 OCH₂CH₂CO₂H N(CH₃)₂ H 6 OCH₂CH₂CO₂CH₂CH₃ N(CH₃)₂ CH₃ 7 OCH₂CH₂CO₂H N(CH₃)₂ CH₃ 8 OCH₂CH₂PO(OCH₂CH₃)₂ N(CH₃)₂ H 9 OCH₂CH₂PO(OH)₂ N(CH₃)₂ H 10 OCH₂CH₂PO(OCH₂CH₃)₂ N(CH₃)₂ CH₃ 11 OCH₂CH₂PO(OH)₂ N(CH₃)₂ CH₃ 12 OCH₂CH═CHCO₂CH₂CH₃ N(CH₃)₂ H 13 OCH₂CH═CHCO₂H N(CH₃)₂ H 14 OCH₂CH═CHCO₂CH₂CH₃ N(CH₃)₂ CH₃ 15 OCH₂CH═CHCO₂H N(CH₃)₂ CH₃ 16 OCH₂C₆H₄CO₂CH₂CH₃(2, 3 or 4) N(CH₃)₂ H 17 OCH₂C₆H₄CO₂H(2, 3 or 4) N(CH₃)₂ H 18 OCH₂C₆H₄CO₂CH₂CH₃(2, 3 or 4) N CH₃ 2 CH₃ 19 OCH₂C₆H₄CO₂H(2, 3 or 4) N(CH₃)₂ CH₃ 20 OCH₂C₆H₄CH₂CO₂CH₂CH₃(2, 3 or 4) N(CH₃)₂ H 21 OCH₂C₆H₄CH₂CO₂H(2, 3 or 4) N(CH₃)₂ H 22 OCH₂C₆H₄CH₂CO₂CH₂CH₃(2, 3 or 4) N(CH₃)₂ CH₃ 23 OCH₂C₆H₄CH₂CO₂H(2, 3 or 4) N(CH₃)₂ CH₃ 24 OCH₂CO₂CH₂CH₃ NHCH₂C₆CH₅ H 25 OCH₂CO₂H NHCH₂C₆CH₅ H 26 OCH₂CO₂CH₂CH₃ NHCH₂C₆CH₅ CH₃ 27 OCH₂CO₂H NHCH₂C₆CH₅ CH₃ 28 OCH₂CH₂CO₂CH₂CH₃ NHCH₂C₆CH₅ H 29 OCH₂CH₂CO₂H NHCH₂C₆CH₅ H 30 OCH₂CH₂CO₂CH₂CH₃ NHCH₂C₆CH₅ CH₃ 31 OCH₂CH₂CO₂H NHCH₂C₆CH₅ CH₃ 32 OCH₂CH₂PO(OCH₂CH₃)₂ NHCH₂C₆CH₅ H 33 OCH₂CH₂PO(OH)₂ NHCH₂C₆CH₅ H 34 OCH₂CH₂PO(OCH₂CH₃)₂ NHCH₂C₆CH₅ CH₃ 35 OCH₂CH₂PO(OH)₂ NHCH₂C₆CH₅ CH₃ 36 OCH₂CH═CHCO₂CH₂CH₃ NHCH₂C₆CH₅ H 37 OCH₂CH═CHCO₂H NHCH₂C₆CH₅ H 38 OCH₂CH═CHCO₂CH₂CH₃ NHCH₂C₆CH₅ CH₃ 39 OCH₂CH═CHCO₂H NHCH₂C₆CH₅ CH₃ 40 OCH₂CO₂CH₂CH₃ NHCH₂CONH₂ H 41 OCH₂CO₂H NHCH₂CONH₂ H 42 OCH₂CO₂CH₂CH₃ NHCH₂CONH₂ CH₃ 43 OCH₂CO₂H NHCH₂CONH₂ CH₃ 44 OCH₂CH₂CO₂CH₂CH₃ NHCH₂CONH₂ H 45 OCH₂CH₂CO₂H NHCH₂CONH₂ H 46 OCH₂CH₂CO₂CH₂CH₃ NHCH₂CONH₂ CH₃ 47 OCH₂CH₂CO₂H NHCH₂CONH₂ CH₃ 48 OCH₂CH₂PO(OCH₂CH₃)₂ NHCH₂CONH₂ H 49 OCH₂CH₂PO(OH)₂ NHCH₂CONH₂ H 50 OCH₂CH₂PO(OCH₂CH₃)₂ NHCH₂CONH₂ CH₃ 51 OCH₂CH₂PO(OH)₂ NHCH₂CONH₂ CH₃ 52 OCH₂CH═CHCO₂CH₂CH₃ NHCH₂CONH₂ H 53 OCH₂CH═CHCO₂H NHCH₂CONH₂ H 54 OCH₂CH═CHCO₂CH₂CH₃ NHCH₂CONH₂ CH₃ 55 OCH₂CH═CHCO₂H NHCH₂CONH₂ CH₃ 56 OCH₂C₆H₄CO₂CH₂CH₃(2, 3 or 4) NHCH₂CONH₂ H 57 OCH₂C₆H₄CO₂H(2, 3 or 4) NHCH₂CONH₂ H 58 OCH₂C₆H₄CO₂CH₂CH₃(2, 3 or 4) NHCH₂CONH₂ CH₃ 59 OCH₂C₆H₄CO₂H(2, 3 or 4) NHCH₂CONH₂ CH₃ 60 OCH₂C₆H₄CH₂CO₂CH₂CH₃(2, 3 or 4) NHCH₂CONH₂ H 61 OCH₂C₆H₄CH₂CO₂H(2, 3 or 4) NHCH₂CONH₂ H 62 OCH₂C₆H₄CH₂CO₂CH₂CH₃(2, 3 or 4) NHCH₂CONH₂ CH₃ 63 OCH₂C₆H₄CH₂CO₂H(2, 3 or 4) NHCH₂CONH₂ CH₃ 64 OCH₂-tetrazole N(CH₃)₂ H 65 OCH₂-tetrazole N(CH₃)₂ CH₃ 66 OCH₂-tetrazole NHCH₂C₆CH₅ H 67 OCH₂-tetrazole NHCH₂C₆CH₅ CH₃ 68 CH₂-tetrazole N(CH₃)₂ H 69 CH₂-tetrazole N(CH₃)₂ CH₃ 70 CH₂-tetrazole NHCH₂C₆CH₅ H 71 CH₂-tetrazole NHCH₂C₆CH₅ CH₃

TABLE IVd

Ex. # X¹ Z R¹ 1 OCH₂CO₂H N(CH₃)₂ H 2 OCH₂CO₂CH₂CH₃ N(CH₃)₂ CH₃ 3 OCH₂CO₂H N(CH₃)₂ CH₃ 4 OCH₂CH₂CO₂CH₂CH₃ N(CH₃)₂ H 5 OCH₂CH₂CO₂H N(CH₃)₂ H 6 OCH₂CH₂CO₂CH₂CH₃ N(CH₃)₂ CH₃ 7 OCH₂CH₂CO₂H N(CH₃)₂ CH₃ 8 OCH₂CH₂PO(OCH₂CH₃)₂ N(CH₃)₂ H 9 OCH₂CH₂PO(OH)₂ N(CH₃)₂ H 10 OCH₂CH₂PO(OCH₂CH₃)₂ N(CH₃)₂ CH₃ 11 OCH₂CH₂PO(OH)₂ N(CH₃)₂ CH₃ 12 OCH₂CH═CHCO₂CH₂CH₃ N(CH₃)₂ H 13 OCH₂CH═CHCO₂H N(CH₃)₂ H 14 OCH₂CH═CHCO₂CH₂CH₃ N(CH₃)₂ CH₃ 15 OCH₂CH═CHCO₂H N(CH₃)₂ CH₃ 16 OCH₂C₆H₄CO₂CH₂CH₃(2, 3 or 4) N(CH₃)₂ H 17 OCH₂C₆H₄CO₂H(2, 3 or 4) N(CH₃)₂ H 18 OCH₂C₆H₄CO₂CH₂CH₃(2, 3 or 4) N(CH₃)₂ CH₃ 19 OCH₂C₆H₄CO₂H(2, 3 or 4) N(CH₃)₂ CH₃ 20 OCH₂C₆H₄CH₂CO₂CH₂CH₃(2, 3 N(CH₃)₂ H or 4) 21 OCH₂C₆H₄CH₂CO₂H(2, 3 or 4) N CH₃ 2 H 22 OCH₂C₆H₄CH₂CO₂CH₂CH₃(2, 3 N(CH₃)₂ CH₃ or 4) 23 OCH₂C₆H₄CH₂CO₂H(2, 3 or 4) N(CH₃)₂ CH₃ 24 OCH₂CO₂CH₂CH₃ NHCH₂C₆CH₅ H 25 OCH₂CO₂H NHCH₂C₆CH₅ H 26 OCH₂CO₂CH₂CH₃ NHCH₂C₆CH₅ CH₃ 27 OCH₂CO₂H NHCH₂C₆CH₅ CH₃ 28 OCH₂CH₂CO₂CH₂CH₃ NHCH₂C₆CH₅ H 29 OCH₂CH₂CO₂H NHCH₂C₆CH₅ H 30 OCH₂CH₂CO₂CH₂CH₃ NHCH₂C₆CH₅ CH₃ 31 OCH₂CH₂CO₂H NHCH₂C₆CH₅ CH₃ 32 OCH₂CH₂PO(OCH₂CH₃)₂ NHCH₂C₆CH₅ H 33 OCH₂CH₂PO(OH)₂ NHCH₂C₆CH₅ H 34 OCH₂CH₂PO(OCH₂CH₃)₂ NHCH₂C₆CH₅ CH₃ 35 OCH₂CH₂PO(OH)₂ NHCH₂C₆CH₅ CH₃ 36 OCH₂CH═CHCO₂CH₂CH₃ NHCH₂C₆CH₅ H 37 OCH₂CH═CHCO₂H NHCH₂C₆CH₅ H 38 OCH₂CH═CHCO₂CH₂CH₃ NHCH₂C₆CH₅ CH₃ 39 OCH₂CH═CHCO₂H NHCH₂C₆CH₅ CH₃ 40 OCH₂CO₂CH₂CH₃ NHCH₂CONH₂ H 41 OCH₂CO₂H NHCH₂CONH₂ H 42 OCH₂CO₂CH₂CH₃ NHCH₂CONH₂ CH₃ 43 OCH₂CO₂H NHCH₂CONH₂ CH₃ 44 OCH₂CH₂CO₂CH₂CH₃ NHCH₂CONH₂ H 45 OCH₂CH₂CO₂H NHCH₂CONH₂ H 46 OCH₂CH₂CO₂CH₂CH₃ NHCH₂CONH₂ CH₃ 47 OCH₂CH₂CO₂H NHCH₂CONH₂ CH₃ 48 OCH₂CH₂PO(OCH₂CH₃)₂ NHCH₂CONH₂ H 49 OCH₂CH₂PO(OH)₂ NHCH₂CONH₂ H 50 OCH₂CH₂PO(OCH₂CH₃)₂ NHCH₂CONH₂ CH₃ 51 OCH₂CH₂PO(OH)₂ NHCH₂CONH₂ CH₃ 52 OCH₂CH═CHCO₂CH₂CH₃ NHCH₂CONH₂ H 53 OCH₂CH═CHCO₂H NHCH₂CONH₂ H 54 OCH₂CH═CHCO₂CH₂CH₃ NHCH₂CONH₂ CH₃ 55 OCH₂CH═CHCO₂H NHCH₂CONH₂ CH₃ 56 OCH₂C₆H₄CO₂CH₂CH₃(2, 3 or 4) NHCH₂CONH₂ H 57 OCH₂C₆H₄CO₂H(2, 3 or 4) NHCH₂CONH₂ H 58 OCH₂C₆H₄CO₂CH₂CH₃(2, 3 or 4) NHCH₂CONH₂ CH₃ 59 OCH₂C₆H₄CO₂H(2, 3 or 4) NHCH₂CONH₂ CH₃ 60 OCH₂C₆H₄CH₂CO₂CH₂CH₃(2, 3 NHCH₂CONH₂ H or 4) 61 OCH₂C₆H₄CH₂CO₂H(2, 3 or 4) NHCH₂CONH₂ H 62 OCH₂C₆H₄CH₂CO₂CH₂CH₃(2, 3 NHCH₂CONH₂ CH₃ or 4) 63 OCH₂C₆H₄CH₂CO₂H(2, 3 or 4) NHCH₂CONH₂ CH₃ 64 OCH₂-tetrazole N(CH₃)₂ H 65 OCH₂-tetrazole N(CH₃)₂ CH₃ 66 OCH₂-tetrazole NHCH₂C₆CH₅ H 67 OCH₂-tetrazole NHCH₂C₆CH₅ CH₃ 68 CH₂-tetrazole N(CH₃)₂ H 69 CH₂-tetrazole N(CH₃)₂ CH₃ 70 CH₂-tetrazole NHCH₂C₆CH₅ H 71 CH₂-tetrazole NHCH₂C₆CH₅ CH₃

TABLE V

Ex. # X X¹ Z R¹ 1. H H OH CO₂CH₂CH₃ 2. H H OH CO₂H 3. H H OH CH₂CO₂CH₂CH₃ 4. H H OH CH₂CO₂H 5. H H OH CH₂CH₂CO₂CH₂CH₃ 6. H H OH CH₂CH₂CO₂H 7. H H OH CH₂CH═CHCO₂H 8. H H OH CH₂CH═CHCO₂H 9. H H OH CH₂CH₂P— O(OCH₂CH₃)₂ 10. H H OH CH₂CH₂P—O(OH)₂ 11. OH H OH CO₂CH₂CH₃ 12. OH H OH CO₂H 13. OH H OH CH₂CO₂CH₂CH₃ 14. OH H OH CH₂CO₂H 15. OH H OH CH₂CH₂CO₂CH₂CH₃ 16. OH H OH CH₂CH₂CO₂H 17. OH H OH CH₂CH═CHCO₂H 18. OH H OH CH₂CH═CHCO₂H 19. OH H OH CH₂CH₂P— O(OCH₂CH₃)₂ 20. OH H OH CH₂CH₂P—O(OH)₂ 21. OCH₃ H OH CO₂CH₂CH₃ 22. OCH₃ H OH CO₂H 23. OCH₃ H OH CH₂CO₂CH₂CH₃ 24. OCH₃ H OH CH₂CO₂H 25. OCH₃ H OH CH₂CH₂CO₂CH₂CH₃ 26. OCH₃ H OH CH₂CH₂CO₂H 27. OCH₃ H OH CH₂CH═CHCO₂H 28. OCH₃ H OH CH₂CH═CHCO₂H 29. OCH₃ H OH CH₂CH₂P— O(OCH₂CH₃)₂ 30. OCH₃ H OH CH₂CH₂P—O(OH)₂ 31. OCH₂CH═CH₂ H OH CO₂CH₂CH₃ 32. OCH₂CH═CH₂ H OH CO₂H 33. OCH₂CH═CH₂ H OH CH₂CO₂CH₂CH₃ 34. OCH₂CH═CH₂ H OH CH₂CO₂H 35. OCH₂CH═CH₂ H OH CH₂CH₂CO₂CH₂CH₃ 36. OCH₂CH═CH₂ H OH CH₂CH₂CO₂H 37. OCH₂CH═CH₂ H OH CH₂CH═CHCO₂H 38. OCH₂CH═CH₂ H OH CH₂CH═CHCO₂H 39. OCH₂CH═CH₂ H OH CH₂CH₂P— O(OCH₂CH₃)₂ 40. OCH₂CH═CH₂ H OH CH₂CH₂P—O(OH)₂ 41. OCH₂C₆H₅ H OH CO₂CH₂CH₃ 42. OCH₂C₆H₅ H OH CO₂H 43. OCH₂C₆H₅ H OH CH₂CO₂CH₂CH₃ 44. OCH₂C₆H₅ H OH CH₂CO₂H 45. OCH₂C₆H₅ H OH CH₂CH₂CO₂CH₂CH₃ 46. OCH₂C₆H₅ H OH CH₂CH₂CO₂H 47. OCH₂C₆H₅ H OH CH₂CH═CHCO₂H 48. OCH₂C₆H₅ H OH CH₂CH═CHCO₂H 49. OCH₂C₆H₅ H OH CH₂CH₂P— O(OCH₂CH₃)₂ 50. OCH₂C₆H₅ H OH CH₂CH₂P—O(OH)₂ 51. Cll H OH CO₂CH₂CH₃ 52. Cl H OH CO₂H 53. Cl H OH CH₂CO₂CH₂CH₃ 54. Cl H OH CH₂CO₂H 55. Cl H OH CH₂CH₂CO₂CH₂CH₃ 56. Cl H OH CH₂CH₂CO₂H 57. Cl H OH CH₂CH═CHCO₂H 58. Cl H OH CH₂CH═CHCO₂H 59. Cl H OH CH₂CH₂P— O(OCH₂CH₃)₂ 60. Cl H OH CH₂CH₂P—O(OH)₂ 61. NO₂ H OH CO₂CH₂CH₃ 62. NO₂ H OH CO₂H 63. NO₂ H OH CH₂CO₂CH₂CH₃ 64. NO₂ H OH CH₂CO₂H 65. NO₂ H OH CH₂CH₂CO₂CH₂CH₃ 66. NO₂ H OH CH₂CH₂CO₂H 67. NO₂ H OH CH₂CH═CHCO₂H 68. NO₂ H OH CH₂CH═CHCO₂H 69. NO₂ H OH CH₂CH₂P— O(OCH₂CH₃)₂ 70. NO₂ H OH CH₂CH₂P—O(OH)₂ 71. NH₂ H OH CO₂CH₂CH₃ 72. NH₂ H OH CO₂H 73. NH₂ H OH CH₂CO₂CH₂CH₃ 74. NH₂ H OH CH₂CO₂H 75. NH₂ H OH CH₂CH₂CO₂CH₂CH₃ 76. NH₂ H OH CH₂CH₂CO₂H 77. NH₂ H OH CH₂CH═CHCO₂H 78. NH₂ H OH CH₂CH═CHCO₂H 79. NH₂ H OH CH₂CH₂P— O(OCH₂CH₃)₂ 80. NH₂ H OH CH₂CH₂P—O(OH)₂ 81. NHSO₂CH₃ H OH H 82. NHSO₂CH₃ H OH CH₃ 83. NHSO₂CH₃ H OH CO₂CH₂CH₃ 84. NHSO₂CH₃ H OH CO₂H 85. NHSO₂CH₃ H OH CH₂CO₂CH₂CH₃ 86. NHSO₂CH₃ H OH CH₂CO₂H 87. NHSO₂CH₃ H OH CH₂CH₂CO₂CH₂CH₃ 88. NHSO₂CH₃ H OH CH₂CH₂CO₂H 89. NHSO₂CH₃ H OH CH₂CH═CHCO₂H 90. NHSO₂CH₃ H OH CH₂CH═CHCO₂H 91. NHSO₂CH₃ H OH CH₂CH₂P— O(OCH₂CH₃)₂ 92. NHSO₂CH₃ H OH CH₂CH₂P—O(OH)₂ 93. OCH₂CONH₂ H OH H 94. OCH₂CONH₂ H OH CH₃ 95. OCH₂CONH₂ H OH CO₂CH₂CH₃ 96. OCH₂CONH₂ H OH CO₂H 97. OCH₂CONH₂ H OH CH₂CO₂CH₂CH₃ 98. OCH₂CONH₂ H OH CH₂CO₂H 99. OCH₂CONH₂ H OH CH₂CH₂CO₂CH₂CH₃ 100. OCH₂CONH₂ H OH CH₂CH₂CO₂H 101. OCH₂CONH₂ H OH CH₂CH═CHCO₂H 102. OCH₂CONH₂ H OH CH₂CH═CHCO₂H 103. OCH₂CONH₂ H OH CH₂CH₂P— O(OCH₂CH₃)₂ 104. OCH₂CONH₂ H OH CH₂CH₂P—O(OH)₂ 105. OH CH₂N(CH₃)₂ OH CO₂CH₂CH₃ 106. OH CH₂N(CH₃)₂ OH CO₂H 107. OH CH₂N(CH₃)₂ OH CH₂CO₂CH₂CH₃ 108. OH CH₂N(CH₃)₂ OH CH₂CO₂H 109. OH CH₂N(CH₃)₂ OH CH₂CH₂CO₂CH₂CH₃ 110. OH CH₂N(CH₃)₂ OH CH₂CH₂CO₂H 111. OH CH₂N(CH₃)₂ OH CH₂CH═CHCO₂H 112. OH CH₂N(CH₃)₂ OH CH₂CH═CHCO₂H 113. OH CH₂N(CH₃)₂ OH CH₂CH₂P— O(OCH₂CH₃)₂ 114. OH CH₂N(CH₃)₂ OH CH₂CH₂P—O(OH)₂ 115. OCH₃ CH₂N(CH₃)₂ OH CO₂CH₂CH₃ 116. OCH₃ CH₂N(CH₃)₂ OH CO₂H 117. OCH₃ CH₂N(CH₃)₂ OH CH₂CO₂CH₂CH₃ 118. OCH₃ CH₂N(CH₃)₂ OH CH₂CO₂H 119. OCH₃ CH₂N(CH₃)₂ OH CH₂CH₂CO₂CH₂CH₃ 120. OCH₃ CH₂N(CH₃)₂ OH CH₂CH₂CO₂H 121. OCH₃ CH₂N(CH₃)₂ OH CH₂CH═CHCO₂H 122. OCH₃ CH₂N(CH₃)₂ OH CH₂CH═CHCO₂H 123. OCH₃ CH₂N(CH₃)₂ OH CH₂CH₂P— O(OCH₂CH₃)₂ 124. OCH₃ CH₂N(CH₃)₂ OH CH₂CH₂P—O(OH)₂ 125. OH CH₂N⁺(CH₃)₃ OH H Cl⁻ 126. OH CH₂N⁺(CH₃)₃ OH CH₃ Cl⁻ 127. OH CH₂N⁺(CH₃)₃ OH CO₂CH₂CH₃ Cl⁻ 128. OH CH₂N⁺(CH₃)₃ OH CO₂H Cl⁻ 129. OH CH₂N⁺(CH₃)₃ OH CH₂CO₂CH₂CH₃ Cl⁻ 130. OH CH₂N⁺(CH₃)₃ OH CH₂CO₂H Cl⁻ 131. OH CH₂N⁺(CH₃)₃ OH CH₂CH₂CO₂CH₂CH₃ Cl⁻ 132. OH CH₂N⁺(CH₃)₃ OH CH₂CH₂CO₂H Cl⁻ 133. OH CH₂N⁺(CH₃)₃ OH CH₂CH═CHCO₂H Cl⁻ 134. OH CH₂N⁺(CH₃)₃ OH CH₂CH═CHCO₂H Cl⁻ 135. OH CH₂N⁺(CH₃)₃ OH CH₂CH₂P— Cl⁻ O(OCH₂CH₃)₂ 136. OH CH₂N⁺(CH₃)₃ OH CH₂CH₂P—O(OH)₂ Cl⁻ 137. OCH₃ CH₂N⁺(CH₃)₃ OH H Cl⁻ 138. OCH₃ CH₂N⁺(CH₃)₃ OH CH₃ Cl⁻ 139. OCH₃ CH₂N⁺(CH₃)₃ OH CO₂CH₂CH₃ Cl⁻ 140. OCH₃ CH₂N⁺(CH₃)₃ OH CO₂H Cl⁻ 141. OCH₃ CH₂N⁺(CH₃)₃ OH CH₂CO₂CH₂CH₃ Cl⁻ 142. OCH₃ CH₂N⁺(CH₃)₃ OH CH₂CO₂H Cl⁻ 143. OCH₃ CH₂N⁺(CH₃)₃ OH CH₂CH₂CO₂CH₂CH₃ Cl⁻ 144. OCH₃ CH₂N⁺(CH₃)₃ OH CH₂CH₂CO₂H Cl⁻ 145. OCH₃ CH₂N⁺(CH₃)₃ OH CH₂CH═CHCO₂H Cl⁻ 146. OCH₃ CH₂N⁺(CH₃)₃ OH CH₂CH═CHCO₂H Cl⁻ 147. OCH₃ CH₂N⁺(CH₃)₃ OH CH₂CH₂P— Cl⁻ O(OCH₂CH₃)₂ 148. OCH₃ CH₂N⁺(CH₃)₃ OH CH₂CH₂P—O(OH)₂ Cl⁻ 149. H H OCH₃ CO₂CH₂CH₃ 150. H H OCH₃ CO₂H 151. H H OCH₃ CH₂CO₂CH₂CH₃ 152. H H OCH₃ CH₂CO₂H 153. H H OCH₃ CH₂CH₂CO₂CH₂CH₃ 154. H H OCH₃ CH₂CH₂CO₂H 155. H H OCH₃ CH₂CH═CHCO₂H 156. H H OCH₃ CH₂CH═CHCO₂H 157. H H OCH₃ CH₂CH₂P— O(OCH₂CH₃)₂ 158. H H OCH₃ CH₂CH₂P—O(OH)₂ 159. OH H OCH₃ CO₂CH₂CH₃ 160. OH H OCH₃ CO₂H 161. OH H OCH₃ CH₂CO₂CH₂CH₃ 162. OH H OCH₃ CH₂CO₂H 163. OH H OCH₃ CH₂CH₂CO₂CH₂CH₃ 164. OH H OCH₃ CH₂CH₂CO₂H 165. OH H OCH₃ CH₂CH═CHCO₂H 166. OH H OCH₃ CH₂CH═CHCO₂H 167. OH H OCH₃ CH₂CH₂P— O(OCH₂CH₃)₂ 168. OH H OCH₃ CH₂CH₂P—O(OH)₂ 169. OCH₃ H OCH₃ CO₂CH₂CH₃ 170. OCH₃ H OCH₃ CO₂H 171. OCH₃ H OCH₃ CH₂CO₂CH₂CH₃ 172. OCH₃ H OCH₃ CH₂CO₂H 173. OCH₃ H OCH₃ CH₂CH₂CO₂CH₂CH₃ 174. OCH₃ H OCH₃ CH₂CH₂CO₂H 175. OCH₃ H OCH₃ CH₂CH═CHCO₂H 176. OCH₃ H OCH₃ CH₂CH═CHCO₂H 177. OCH₃ H OCH₃ CH₂CH₂P— O(OCH₂CH₃)₂ 178. OCH₃ H OCH₃ CH₂CH₂P—O(OH)₂ 179. OCH₂CH═CH₂ H OCH₃ CO₂CH₂CH₃ 180. OCH₂CH═CH₂ H OCH₃ CO₂H 181. OCH₂CH═CH₂ H OCH₃ CH₂CO₂CH₂CH₃ 182. OCH₂CH═CH₂ H OCH₃ CH₂CO₂H 183. OCH₂CH═CH₂ H OCH₃ CH₂CH₂CO₂CH₂CH₃ 184. OCH₂CH═CH₂ H OCH₃ CH₂CH₂CO₂H 185. OCH₂CH═CH₂ H OCH₃ CH₂CH═CHCO₂H 186. OCH₂CH═CH₂ H OCH₃ CH₂CH═CHCO₂H 187. OCH₂CH═CH₂ H OCH₃ CH₂CH₂P— O(OCH₂CH₃)₂ 188. OCH₂CH═CH₂ H OCH₃ CH₂CH₂P—O(OH)₂ 189. OCH₂C₆H₅ H OCH₃ CO₂CH₂CH₃ 190. OCH₂C₆H₅ H OCH₃ CO₂H 191. OCH₂C₆H₅ H OCH₃ CH₂CO₂CH₂CH₃ 192. OCH₂C₆H₅ H OCH₃ CH₂CO₂H 193. OCH₂C₆H₅ H OCH₃ CH₂CH₂CO₂CH₂CH₃ 194. OCH₂C₆H₅ H OCH₃ CH₂CH₂CO₂H 195. OCH₂C₆H₅ H OCH₃ CH₂CH═CHCO₂H 196. OCH₂C₆H₅ H OCH₃ CH₂CH═CHCO₂H 197. OCH₂C₆H₅ H OCH₃ CH₂CH₂P— O(OCH₂CH₃)₂ 198. OCH₂C₆H₅ H OCH₃ CH₂CH₂P—O(OH)₂ 199. Cl H OCH₃ CO₂CH₂CH₃ 200. Cl H OCH₃ CO₂H 201. Cl H OCH₃ CH₂CO₂CH₂CH₃ 202. Cl H OCH₃ CH₂CO₂H 203. Cl H OCH₃ CH₂CH₂CO₂CH₂CH₃ 204. Cl H OCH₃ CH₂CH₂CO₂H 205. Cl H OCH₃ CH₂CH═CHCO₂H 206. Cl H OCH₃ CH₂CH═CHCO₂H 207. Cl H OCH₃ CH₂CH₂P— O(OCH₂CH₃)₂ 208. Cl H OCH₃ CH₂CH₂P—O(OH)₂ 209. NO₂ H OCH₃ CO₂CH₂CH₃ 210. NO₂ H OCH₃ CO₂H 211. NO₂ H OCH₃ CH₂CO₂CH₂CH₃ 212. NO₂ H OCH₃ CH₂CO₂H 213. NO₂ H OCH₃ CH₂CH₂CO₂CH₂CH₃ 214. NO₂ H OCH₃ CH₂CH₂CO₂H 215. NO₂ H OCH₃ CH₂CH═CHCO₂H 216. NO₂ H OCH₃ CH₂CH═CHCO₂H 217. NO₂ H OCH₃ CH₂CH₂P— O(OCH₂CH₃)₂ 218. NO₂ H OCH₃ CH₂CH₂P—O(OH)₂ 219. NH₂ H OCH₃ CO₂CH₂CH₃ 220. NH₂ H OCH₃ CO₂H 221. NH₂ H OCH₃ CH₂CO₂CH₂CH₃ 222. NH₂ H OCH₃ CH₂CO₂H 223. NH₂ H OCH₃ CH₂CH₂CO₂CH₂CH₃ 224. NH₂ H OCH₃ CH₂CH₂CO₂H 225. NH₂ H OCH₃ CH₂CH═CHCO₂H 226. NH₂ H OCH₃ CH₂CH═CHCO₂H 227. NH₂ H OCH₃ CH₂CH₂P— O(OCH₂CH₃)₂ 228. NH₂ H OCH₃ CH₂CH₂P—O(OH)₂ 229. NHSO₂CH₃ H OCH₃ H 230. NHSO₂CH₃ H OCH₃ CH₃ 231. NHSO₂CH₃ H OCH₃ CO₂CH₂CH₃ 232. NHSO₂CH₃ H OCH₃ CO₂H 233. NHSO₂CH₃ H OCH₃ CH₂CO₂CH₂CH₃ 234. NHSO₂CH₃ H OCH₃ CH₂CO₂H 235. NHSO₂CH₃ H OCH₃ CH₂CH₂CO₂CH₂CH₃ 236. NHSO₂CH₃ H OCH₃ CH₂CH₂CO₂H 237. NHSO₂CH₃ H OCH₃ CH₂CH═CHCO₂H 238. NHSO₂CH₃ H OCH₃ CH₂CH═CHCO₂H 239. NHSO₂CH₃ H OCH₃ CH₂CH₂P— O(OCH₂CH₃)₂ 240. NHSO₂CH₃ H OCH₃ CH₂CH₂P—O(OH)₂ 241. OCH₂CONH₂ H OCH₃ H 242. OCH₂CONH₂ H OCH₃ CH₃ 243. OCH₂CONH₂ H OCH₃ CO₂CH₂CH₃ 244. OCH₂CONH₂ H OCH₃ CO₂H 245. OCH₂CONH₂ H OCH₃ CH₂CO₂CH₂CH₃ 246. OCH₂CONH₂ H OCH₃ CH₂CO₂H 247. OCH₂CONH₂ H OCH₃ CH₂CH₂CO₂CH₂CH₃ 248. OCH₂CONH₂ H OCH₃ CH₂CH₂CO₂H 249. OCH₂CONH₂ H OCH₃ CH₂CH═CHCO₂H 250. OCH₂CONH₂ H OCH₃ CH₂CH═CHCO₂H 251. OCH₂CONH₂ H OCH₃ CH₂CH₂P— O(OCH₂CH₃)₂ 252. OCH₂CONH₂ H OCH₃ CH₂CH₂P—O(OH)₂ 253. OH CH₂N(CH₃)₂ OCH₃ CO₂CH₂CH₃ 254. OH CH₂N(CH₃)₂ OCH₃ CO₂H 255. OH CH₂N(CH₃)₂ OCH₃ CH₂CO₂CH₂CH₃ 256. OH CH₂N(CH₃)₂ OCH₃ CH₂CO₂H 257. OH CH₂N(CH₃)₂ OCH₃ CH₂CH₂CO₂CH₂CH₃ 258. OH CH₂N(CH₃)₂ OCH₃ CH₂CH₂CO₂H 259. OH CH₂N(CH₃)₂ OCH₃ CH₂CH═CHCO₂H 260. OH CH₂N(CH₃)₂ OCH₃ CH₂CH═CHCO₂H 261. OH CH₂N(CH₃)₂ OCH₃ CH₂CH₂P— O(OCH₂CH₃)₂ 262. OH CH₂N(CH₃)₂ OCH₃ CH₂CH₂P—O(OH)₂ 263. OCH₃ CH₂N(CH₃)₂ OCH₃ CO₂CH₂CH₃ 264. OCH₃ CH₂N(CH₃)₂ OCH₃ CO₂H 265. OCH₃ CH₂N(CH₃)₂ OCH₃ CH₂CO₂CH₂CH₃ 266. OCH₃ CH₂N(CH₃)₂ OCH₃ CH₂CO₂H 267. OCH₃ CH₂N(CH₃)₂ OCH₃ CH₂CH₂CO₂CH₂CH₃ 268. OCH₃ CH₂N(CH₃)₂ OCH₃ CH₂CH₂CO₂H 269. OCH₃ CH₂N(CH₃)₂ OCH₃ CH₂CH═CHCO₂H 270. OCH₃ CH₂N(CH₃)₂ OCH₃ CH₂CH═CHCO₂H 271. OCH₃ CH₂N(CH₃)₂ OCH₃ CH₂CH₂P— O(OCH₂CH₃)₂ 272. OCH₃ CH₂N(CH₃)₂ OCH₃ CH₂CH₂P—O(OH)₂ 273. OH CH₂N⁺(CH₃)₃ OCH₃ H Cl⁻ 274. OH CH₂N⁺(CH₃)₃ OCH₃ CH₃ Cl⁻ 275. OH CH₂N⁺(CH₃)₃ OCH₃ CO₂CH₂CH₃ Cl⁻ 276. OH CH₂N⁺(CH₃)₃ OCH₃ CO₂H Cl⁻ 277. OH CH₂N⁺(CH₃)₃ OCH₃ CH₂CO₂CH₂CH₃ Cl⁻ 278. OH CH₂N⁺(CH₃)₃ OCH₃ CH₂CO₂H Cl⁻ 279. OH CH₂N⁺(CH₃)₃ OCH₃ CH₂CH₂CO₂CH₂CH₃ Cl⁻ 280. OH CH₂N⁺(CH₃)₃ OCH₃ CH₂CH₂CO₂H Cl⁻ 281. OH CH₂N⁺(CH₃)₃ OCH₃ CH₂CH═CHCO₂H Cl⁻ 282. OH CH₂N⁺(CH₃)₃ OCH₃ CH₂CH═CHCO₂H Cl⁻ 283. OH CH₂N⁺(CH₃)₃ OCH₃ CH₂CH₂P— Cl⁻ O(OCH₂CH₃)₂ 284. OH CH₂N⁺(CH₃)₃ OCH₃ CH₂CH₂P—O(OH)₂ Cl⁻ 285. OCH₃ CH₂N⁺(CH₃)₃ OCH₃ H Cl⁻ 286. OCH₃ CH₂N⁺(CH₃)₃ OCH₃ CH₃ Cl⁻ 287. OCH₃ CH₂N⁺(CH₃)₃ OCH₃ CO₂CH₂CH₃ Cl⁻ 288. OCH₃ CH₂N⁺(CH₃)₃ OCH₃ CO₂H Cl⁻ 289. OCH₃ CH₂N⁺(CH₃)₃ OCH₃ CH₂CO₂CH₂CH₃ Cl⁻ 290. OCH₃ CH₂N⁺(CH₃)₃ OCH₃ CH₂CO₂H Cl⁻ 291. OCH₃ CH₂N⁺(CH₃)₃ OCH₃ CH₂CH₂CO₂CH₂CH₃ Cl⁻ 292. OCH₃ CH₂N⁺(CH₃)₃ OCH₃ CH₂CH₂CO₂H Cl⁻ 293. OCH₃ CH₂N⁺(CH₃)₃ OCH₃ CH₂CH═CHCO₂H Cl⁻ 294. OCH₃ CH₂N⁺(CH₃)₃ OCH₃ CH₂CH═CHCO₂H Cl⁻ 295. OCH₃ CH₂N⁺(CH₃)₃ OCH₃ CH₂CH₂P— Cl⁻ O(OCH₂CH₃)₂ 296. OCH₃ CH₂N⁺(CH₃)₃ OCH₃ CH₂CH₂P—O(OH)₂ Cl⁻ 297. H H OCH₂C₆H₅ CO₂CH₂CH₃ 298. H H OCH₂C₆H₅ CO₂H 299. H H OCH₂C₆H₅ CH₂CO₂CH₂CH₃ 300. H H OCH₂C₆H₅ CH₂CO₂H 301. H H OCH₂C₆H₅ CH₂CH₂CO₂CH₂CH₃ 302. H H OCH₂C₆H₅ CH₂CH₂CO₂H 303. H H OCH₂C₆H₅ CH₂CH═CHCO₂H 304. H H OCH₂C₆H₅ CH₂CH═CHCO₂H 305. H H OCH₂C₆H₅ CH₂CH₂P— O(OCH₂CH₃)₂ 306. H H OCH₂C₆H₅ CH₂CH₂P—O(OH)₂ 307. OH H OCH₂C₆H₅ CO₂CH₂CH₃ 308. OH H OCH₂C₆H₅ CO₂H 309. OH H OCH₂C₆H₅ CH₂CO₂CH₂CH₃ 310. OH H OCH₂C₆H₅ CH₂CO₂H 311. OH H OCH₂C₆H₅ CH₂CH₂CO₂CH₂CH₃ 312. OH H OCH₂C₆H₅ CH₂CH₂CO₂H 313. OH H OCH₂C₆H₅ CH₂CH═CHCO₂H 314. OH H OCH₂C₆H₅ CH₂CH═CHCO₂H 315. OH H OCH₂C₆H₅ CH₂CH₂P— O(OCH₂CH₃)₂ 316. OH H OCH₂C₆H₅ CH₂CH₂P—O(OH)₂ 317. OCH₃ H OCH₂C₆H₅ CO₂CH₂CH₃ 318. OCH₃ H OCH₂C₆H₅ CO₂H 319. OCH₃ H OCH₂C₆H₅ CH₂CO₂CH₂CH₃ 320. OCH₃ H OCH₂C₆H₅ CH₂CO₂H 321. OCH₃ H OCH₂C₆H₅ CH₂CH₂CO₂CH₂CH₃ 322. OCH₃ H OCH₂C₆H₅ CH₂CH₂CO₂H 323. OCH₃ H OCH₂C₆H₅ CH₂CH═CHCO₂H 324. OCH₃ H OCH₂C₆H₅ CH₂CH═CHCO₂H 325. OCH₃ H OCH₂C₆H₅ CH₂CH₂P— O(OCH₂CH₃)₂ 326. OCH₃ H OCH₂C₆H₅ CH₂CH₂P—O(OH)₂ 327. OCH₂CH═CH₂ H OCH₂C₆H₅ CO₂CH₂CH₃ 328. OCH₂CH═CH₂ H OCH₂C₆H₅ CO₂H 329. OCH₂CH═CH₂ H OCH₂C₆H₅ CH₂CO₂CH₂CH₃ 330. OCH₂CH═CH₂ H OCH₂C₆H₅ CH₂CO₂H 331. OCH₂CH═CH₂ H OCH₂C₆H₅ CH₂CH₂CO₂CH₂CH₃ 332. OCH₂CH═CH₂ H OCH₂C₆H₅ CH₂CH₂CO₂H 333. OCH₂CH═CH₂ H OCH₂C₆H₅ CH₂CH═CHCO₂H 334. OCH₂CH═CH₂ H OCH₂C₆H₅ CH₂CH═CHCO₂H 335. OCH₂CH═CH₂ H OCH₂C₆H₅ CH₂CH₂P— O(OCH₂CH₃)₂ 336. OCH₂CH═CH₂ H OCH₂C₆H₅ CH₂CH₂P—O(OH)₂ 337. OCH₂C₆H₅ H OCH₂C₆H₅ CO₂CH₂CH₃ 338. OCH₂C₆H₅ H OCH₂C₆H₅ CO₂H 339. OCH₂C₆H₅ H OCH₂C₆H₅ CH₂CO₂CH₂CH₃ 340. OCH₂C₆H₅ H OCH₂C₆H₅ CH₂CO₂H 341. OCH₂C₆H₅ H OCH₂C₆H₅ CH₂CH₂CO₂CH₂CH₃ 342. OCH₂C₆H₅ H OCH₂C₆H₅ CH₂CH₂CO₂H 343. OCH₂C₆H₅ H OCH₂C₆H₅ CH₂CH═CHCO₂H 344. OCH₂C₆H₅ H OCH₂C₆H₅ CH₂CH═CHCO₂H 345. OCH₂C₆H₅ H OCH₂C₆H₅ CH₂CH₂P— O(OCH₂CH₃)₂ 346. OCH₂C₆H₅ H OCH₂C₆H₅ CH₂CH₂P—O(OH)₂ 347. Cl H OCH₂C₆H₅ CO₂CH₂CH₃ 348. Cl H OCH₂C₆H₅ CO₂H 349. Cl H OCH₂C₆H₅ CH₂CO₂CH₂CH₃ 350. Cl H OCH₂C₆H₅ CH₂CO₂H 351. Cl H OCH₂C₆H₅ CH₂CH₂CO₂CH₂CH₃ 352. Cl H OCH₂C₆H₅ CH₂CH₂CO₂H 353. Cl H OCH₂C₆H₅ CH₂CH═CHCO₂H 354. Cl H OCH₂C₆H₅ CH₂CH═CHCO₂H 355. Cl H OCH₂C₆H₅ CH₂CH₂P— O(OCH₂CH₃)₂ 356. Cl H OCH₂C₆H₅ CH₂CH₂P—O(OH)₂ 357. NO₂ H OCH₂C₆H₅ CO₂CH₂CH₃ 358. NO₂ H OCH₂C₆H₅ CO₂H 359. NO₂ H OCH₂C₆H₅ CH₂CO₂CH₂CH₃ 360. NO₂ H OCH₂C₆H₅ CH₂CO₂H 361. NO₂ H OCH₂C₆H₅ CH₂CH₂CO₂CH₂CH₃ 362. NO₂ H OCH₂C₆H₅ CH₂CH₂CO₂H 363. NO₂ H OCH₂C₆H₅ CH₂CH═CHCO₂H 364. NO₂ H OCH₂C₆H₅ CH₂CH═CHCO₂H 365. NO₂ H OCH₂C₆H₅ CH₂CH₂P— O(OCH₂CH₃)₂ 366. NO₂ H OCH₂C₆H₅ CH₂CH₂P—O(OH)₂ 367. NH₂ H OCH₂C₆H₅ CO₂CH₂CH₃ 368. NH₂ H OCH₂C₆H₅ CO₂H 369. NH₂ H OCH₂C₆H₅ CH₂CO₂CH₂CH₃ 370. NH₂ H OCH₂C₆H₅ CH₂CO₂H 371. NH₂ H OCH₂C₆H₅ CH₂CH₂CO₂CH₂CH₃ 372. NH₂ H OCH₂C₆H₅ CH₂CH₂CO₂H 373. NH₂ H OCH₂C₆H₅ CH₂CH═CHCO₂H 374. NH₂ H OCH₂C₆H₅ CH₂CH═CHCO₂H 375. NH₂ H OCH₂C₆H₅ CH₂CH₂P— O(OCH₂CH₃)₂ 376. NH₂ H OCH₂C₆H₅ CH₂CH₂P—O(OH)₂ 377. NHSO₂CH₃ H OCH₂C₆H₅ H 378. NHSO₂CH₃ H OCH₂C₆H₅ CH₃ 379. NHSO₂CH₃ H OCH₂C₆H₅ CO₂CH₂CH₃ 380. NHSO₂CH₃ H OCH₂C₆H₅ CO₂H 381. NHSO₂CH₃ H OCH₂C₆H₅ CH₂CO₂CH₂CH₃ 382. NHSO₂CH₃ H OCH₂C₆H₅ CH₂CO₂H 383. NHSO₂CH₃ H OCH₂C₆H₅ CH₂CH₂CO₂CH₂CH₃ 384. NHSO₂CH₃ H OCH₂C₆H₅ CH₂CH₂CO₂H 385. NHSO₂CH₃ H OCH₂C₆H₅ CH₂CH═CHCO₂H 386. NHSO₂CH₃ H OCH₂C₆H₅ CH₂CH═CHCO₂H 387. NHSO₂CH₃ H OCH₂C₆H₅ CH₂CH₂P— O(OCH₂CH₃)₂ 388. NHSO₂CH₃ H OCH₂C₆H₅ CH₂CH₂P—O(OH)₂ 389. OCH₂CONH₂ H OCH₂C₆H₅ H 390. OCH₂CONH₂ H OCH₂C₆H₅ CH₃ 391. OCH₂CONH₂ H OCH₂C₆H₅ CO₂CH₂CH₃ 392. OCH₂CONH₂ H OCH₂C₆H₅ CO₂H 393. OCH₂CONH₂ H OCH₂C₆H₅ CH₂CO₂CH₂CH₃ 394. OCH₂CONH₂ H OCH₂C₆H₅ CH₂CO₂H 395. OCH₂CONH₂ H OCH₂C₆H₅ CH₂CH₂CO₂CH₂CH₃ 396. OCH₂CONH₂ H OCH₂C₆H₅ CH₂CH₂CO₂H 397. OCH₂CONH₂ H OCH₂C₆H₅ CH₂CH═CHCO₂H 398. OCH₂CONH₂ H OCH₂C₆H₅ CH₂CH═CHCO₂H 399. OCH₂CONH₂ H OCH₂C₆H₅ CH₂CH₂P— O(OCH₂CH₃)₂ 400. OCH₂CONH₂ H OCH₂C₆H₅ CH₂CH₂P—O(OH)₂ 401. OH CH₂N(CH₃)₂ OCH₂C₆H₅ CO₂CH₂CH₃ 402. OH CH₂N(CH₃)₂ OCH₂C₆H₅ CO₂H 403. OH CH₂N(CH₃)₂ OCH₂C₆H₅ CH₂CO₂CH₂CH₃ 404. OH CH₂N(CH₃)₂ OCH₂C₆H₅ CH₂CO₂H 405. OH CH₂N(CH₃)₂ OCH₂C₆H₅ CH₂CH₂CO₂CH₂CH₃ 406. OH CH₂N(CH₃)₂ OCH₂C₆H₅ CH₂CH₂CO₂H 407. OH CH₂N(CH₃)₂ OCH₂C₆H₅ CH₂CH═CHCO₂H 408. OH CH₂N(CH₃)₂ OCH₂C₆H₅ CH₂CH═CHCO₂H 409. OH CH₂N(CH₃)₂ OCH₂C₆H₅ CH₂CH₂P— O(OCH₂CH₃)₂ 410. OH CH₂N(CH₃)₂ OCH₂C₆H₅ CH₂CH₂P—O(OH)₂ 411. OCH₃ CH₂N(CH₃)₂ OCH₂C₆H₅ CO₂CH₂CH₃ 412. OCH₃ CH₂N(CH₃)₂ OCH₂C₆H₅ CO₂H 413. OCH₃ CH₂N(CH₃)₂ OCH₂C₆H₅ CH₂CO₂CH₂CH₃ 414. OCH₃ CH₂N(CH₃)₂ OCH₂C₆H₅ CH₂CO₂H 415. OCH₃ CH₂N(CH₃)₂ OCH₂C₆H₅ CH₂CH₂CO₂CH₂CH₃ 416. OCH₃ CH₂N(CH₃)₂ OCH₂C₆H₅ CH₂CH₂CO₂H 417. OCH₃ CH₂N(CH₃)₂ OCH₂C₆H₅ CH₂CH═CHCO₂H 418. OCH₃ CH₂N(CH₃)₂ OCH₂C₆H₅ CH₂CH═CHCO₂H 419. OCH₃ CH₂N(CH₃)₂ OCH₂C₆H₅ CH₂CH₂P— O(OCH₂CH₃)₂ 420. OCH₃ CH₂N(CH₃)₂ OCH₂C₆H₅ CH₂CH₂P—O(OH)₂ 421. OH CH₂N⁺(CH₃)₃ OCH₂C₆H₅ H Cl⁻ 422. OH CH₂N⁺(CH₃)₃ OCH₂C₆H₅ CH₃ Cl⁻ 423. OH CH₂N⁺(CH₃)₃ OCH₂C₆H₅ CO₂CH₂CH₃ Cl⁻ 424. OH CH₂N⁺(CH₃)₃ OCH₂C₆H₅ CO₂H Cl⁻ 425. OH CH₂N⁺(CH₃)₃ OCH₂C₆H₅ CH₂CO₂CH₂CH₃ Cl⁻ 426. OH CH₂N⁺(CH₃)₃ OCH₂C₆H₅ CH₂CO₂H Cl⁻ 427. OH CH₂N⁺(CH₃)₃ OCH₂C₆H₅ CH₂CH₂CO₂CH₂CH₃ Cl⁻ 428. OH CH₂N⁺(CH₃)₃ OCH₂C₆H₅ CH₂CH₂CO₂H Cl⁻ 429. OH CH₂N⁺(CH₃)₃ OCH₂C₆H₅ CH₂CH═CHCO₂H Cl⁻ 430. OH CH₂N⁺(CH₃)₃ OCH₂C₆H₅ CH₂CH═CHCO₂H Cl⁻ 431. OH CH₂N⁺(CH₃)₃ OCH₂C₆H₅ CH₂CH₂P— Cl⁻ O(OCH₂CH₃)₂ 432. OH CH₂N⁺(CH₃)₃ OCH₂C₆H₅ CH₂CH₂P—O(OH)₂ Cl⁻ 433. OCH₃ CH₂N⁺(CH₃)₃ OCH₂C₆H₅ H Cl⁻ 434. OCH₃ CH₂N⁺(CH₃)₃ OCH₂C₆H₅ CH₃ Cl⁻ 435. OCH₃ CH₂N⁺(CH₃)₃ OCH₂C₆H₅ CO₂CH₂CH₃ Cl⁻ 436. OCH₃ CH₂N⁺(CH₃)₃ OCH₂C₆H₅ CO₂H Cl⁻ 437. OCH₃ CH₂N⁺(CH₃)₃ OCH₂C₆H₅ CH₂CO₂CH₂CH₃ Cl⁻ 438. OCH₃ CH₂N⁺(CH₃)₃ OCH₂C₆H₅ CH₂CO₂H Cl⁻ 439. OCH₃ CH₂N⁺(CH₃)₃ OCH₂C₆H₅ CH₂CH₂CO₂CH₂CH₃ Cl⁻ 440. OCH₃ CH₂N⁺(CH₃)₃ OCH₂C₆H₅ CH₂CH₂CO₂H Cl⁻ 441. OCH₃ CH₂N⁺(CH₃)₃ OCH₂C₆H₅ CH₂CH═CHCO₂H Cl⁻ 442. OCH₃ CH₂N⁺(CH₃)₃ OCH₂C₆H₅ CH₂CH═CHCO₂H Cl⁻ 443. OCH₃ CH₂N⁺(CH₃)₃ OCH₂C₆H₅ CH₂CH₂P— Cl⁻ O(OCH₂CH₃)₂ 444. OCH₃ CH₂N⁺(CH₃)₃ OCH₂C₆H₅ CH₂CH₂P—O(OH)₂ Cl⁻ 445. H H OCH₂CH═CH₂ CO₂CH₂CH₃ 446. H H OCH₂CH═CH₂ CO₂H 447. H H OCH₂CH═CH₂ CH₂CO₂CH₂CH₃ 448. H H OCH₂CH═CH₂ CH₂CO₂H 449. H H OCH₂CH═CH₂ CH₂CH₂CO₂CH₂CH₃ 450. H H OCH₂CH═CH₂ CH₂CH₂CO₂H 451. H H OCH₂CH═CH₂ CH₂CH═CHCO₂H 452. H H OCH₂CH═CH₂ CH₂CH═CHCO₂H 453. H H OCH₂CH═CH₂ CH₂CH₂P— O(OCH₂CH₃)₂ 454. H H OCH₂CH═CH₂ CH₂CH₂P—O(OH)₂ 455. OH H OCH₂CH═CH₂ CO₂CH₂CH₃ 456. OH H OCH₂CH═CH₂ CO₂H 457. OH H OCH₂CH═CH₂ CH₂CO₂CH₂CH₃ 458. OH H OCH₂CH═CH₂ CH₂CO₂H 459. OH H OCH₂CH═CH₂ CH₂CH₂CO₂CH₂CH₃ 460. OH H OCH₂CH═CH₂ CH₂CH₂CO₂H 461. OH H OCH₂CH═CH₂ CH₂CH═CHCO₂H 462. OH H OCH₂CH═CH₂ CH₂CH═CHCO₂H 463. OH H OCH₂CH═CH₂ CH₂CH₂P— O(OCH₂CH₃)₂ 464. OH H OCH₂CH═CH₂ CH₂CH₂P—O(OH)₂ 465. OCH₃ H OCH₂CH═CH₂ CO₂CH₂CH₃ 466. OCH₃ H OCH₂CH═CH₂ CO₂H 467. OCH₃ H OCH₂CH═CH₂ CH₂CO₂CH₂CH₃ 468. OCH₃ H OCH₂CH═CH₂ CH₂CO₂H 469. OCH₃ H OCH₂CH═CH₂ CH₂CH₂CO₂CH₂CH₃ 470. OCH₃ H OCH₂CH═CH₂ CH₂CH₂CO₂H 471. OCH₃ H OCH₂CH═CH₂ CH₂CH═CHCO₂H 472. OCH₃ H OCH₂CH═CH₂ CH₂CH═CHCO₂H 473. OCH₃ H OCH₂CH═CH₂ CH₂CH₂P— O(OCH₂CH₃)₂ 474. OCH₃ H OCH₂CH═CH₂ CH₂CH₂P—O(OH)₂ 475. OCH₂CH═CH₂ H OCH₂CH═CH₂ CO₂CH₂CH₃ 476. OCH₂CH═CH₂ H OCH₂CH═CH₂ CO₂H 477. OCH₂CH═CH₂ H OCH₂CH═CH₂ CH₂CO₂CH₂CH₃ 478. OCH₂CH═CH₂ H OCH₂CH═CH₂ CH₂CO₂H 479. OCH₂CH═CH₂ H OCH₂CH═CH₂ CH₂CH₂CO₂CH₂CH₃ 480. OCH₂CH═CH₂ H OCH₂CH═CH₂ CH₂CH₂CO₂H 481. OCH₂CH═CH₂ H OCH₂CH═CH₂ CH₂CH═CHCO₂H 482. OCH₂CH═CH₂ H OCH₂CH═CH₂ CH₂CH═CHCO₂H 483. OCH₂CH═CH₂ H OCH₂CH═CH₂ CH₂CH₂P— O(OCH₂CH₃)₂ 484. OCH₂CH═CH₂ H OCH₂CH═CH₂ CH₂CH₂P—O(OH)₂ 485. OCH₂C₆H₅ H OCH₂CH═CH₂ CO₂CH₂CH₃ 486. OCH₂C₆H₅ H OCH₂CH═CH₂ CO₂H 487. OCH₂C₆H₅ H OCH₂CH═CH₂ CH₂CO₂CH₂CH₃ 488. OCH₂C₆H₅ H OCH₂CH═CH₂ CH₂CO₂H 489. OCH₂C₆H₅ H OCH₂CH═CH₂ CH₂CH₂CO₂CH₂CH₃ 490. OCH₂C₆H₅ H OCH₂CH═CH₂ CH₂CH₂CO₂H 491. OCH₂C₆H₅ H OCH₂CH═CH₂ CH₂CH═CHCO₂H 492. OCH₂C₆H₅ H OCH₂CH═CH₂ CH₂CH═CHCO₂H 493. OCH₂C₆H₅ H OCH₂CH═CH₂ CH₂CH₂P— O(OCH₂CH₃)₂ 494. OCH₂C₆H₅ H OCH₂CH═CH₂ CH₂CH₂P—O(OH)₂ 495. Cll H OCH₂CH═CH₂ CO₂CH₂CH₃ 496. Cl H OCH₂CH═CH₂ CO₂H 497. Cl H OCH₂CH═CH₂ CH₂CO₂CH₂CH₃ 498. Cl H OCH₂CH═CH₂ CH₂CO₂H 499. Cl H OCH₂CH═CH₂ CH₂CH₂CO₂CH₂CH₃ 500. Cl H OCH₂CH═CH₂ CH₂CH₂CO₂H 501. Cl H OCH₂CH═CH₂ CH₂CH═CHCO₂H 502. Cl H OCH₂CH═CH₂ CH₂CH═CHCO₂H 503. Cl H OCH₂CH═CH₂ CH₂CH₂P— O(OCH₂CH₃)₂ 504. Cl H OCH₂CH═CH₂ CH₂CH₂P—O(OH)₂ 505. NO₂ H OCH₂CH═CH₂ CO₂CH₂CH₃ 506. NO₂ H OCH₂CH═CH₂ CO₂H 507. NO₂ H OCH₂CH═CH₂ CH₂CO₂CH₂CH₃ 508. NO₂ H OCH₂CH═CH₂ CH₂CO₂H 509. NO₂ H OCH₂CH═CH₂ CH₂CH₂CO₂CH₂CH₃ 510. NO₂ H OCH₂CH═CH₂ CH₂CH₂CO₂H 511. NO₂ H OCH₂CH═CH₂ CH₂CH═CHCO₂H 512. NO₂ H OCH₂CH═CH₂ CH₂CH═CHCO₂H 513. NO₂ H OCH₂CH═CH₂ CH₂CH₂P— O(OCH₂CH₃)₂ 514. NO₂ H OCH₂CH═CH₂ CH₂CH₂P—O(OH)₂ 515. NH₂ H OCH₂CH═CH₂ CO₂CH₂CH₃ 516. NH₂ H OCH₂CH═CH₂ CO₂H 517. NH₂ H OCH₂CH═CH₂ CH₂CO₂CH₂CH₃ 518. NH₂ H OCH₂CH═CH₂ CH₂CO₂H 519. NH₂ H OCH₂CH═CH₂ CH₂CH₂CO₂CH₂CH₃ 520. NH₂ H OCH₂CH═CH₂ CH₂CH₂CO₂H 521. NH₂ H OCH₂CH═CH₂ CH₂CH═CHCO₂H 522. NH₂ H OCH₂CH═CH₂ CH₂CH═CHCO₂H 523. NH₂ H OCH₂CH═CH₂ CH₂CH₂P— O(OCH₂CH₃)₂ 524. NH₂ H OCH₂CH═CH₂ CH₂CH₂P—O(OH)₂ 525. NHSO₂CH₃ H OCH₂CH═CH₂ H 526. NHSO₂CH₃ H OCH₂CH═CH₂ CH₃ 527. NHSO₂CH₃ H OCH₂CH═CH₂ CO₂CH₂CH₃ 528. NHSO₂CH₃ H OCH₂CH═CH₂ CO₂H 529. NHSO₂CH₃ H OCH₂CH═CH₂ CH₂CO₂CH₂CH₃ 530. NHSO₂CH₃ H OCH₂CH═CH₂ CH₂CO₂H 531. NHSO₂CH₃ H OCH₂CH═CH₂ CH₂CH₂CO₂CH₂CH₃ 532. NHSO₂CH₃ H OCH₂CH═CH₂ CH₂CH₂CO₂H 533. NHSO₂CH₃ H OCH₂CH═CH₂ CH₂CH═CHCO₂H 534. NHSO₂CH₃ H OCH₂CH═CH₂ CH₂CH═CHCO₂H 535. NHSO₂CH₃ H OCH₂CH═CH₂ CH₂CH₂P— O(OCH₂CH₃)₂ 536. NHSO₂CH₃ H OCH₂CH═CH₂ CH₂CH₂P—O(OH)₂ 537. OCH₂CONH₂ H OCH₂CH═CH₂ H 538. OCH₂CONH₂ H OCH₂CH═CH₂ CH₃ 539. OCH₂CONH₂ H OCH₂CH═CH₂ CO₂CH₂CH₃ 540. OCH₂CONH₂ H OCH₂CH═CH₂ CO₂H 541. OCH₂CONH₂ H OCH₂CH═CH₂ CH₂CO₂CH₂CH₃ 542. OCH₂CONH₂ H OCH₂CH═CH₂ CH₂CO₂H 543. OCH₂CONH₂ H OCH₂CH═CH₂ CH₂CH₂CO₂CH₂CH₃ 544. OCH₂CONH₂ H OCH₂CH═CH₂ CH₂CH₂CO₂H 545. OCH₂CONH₂ H OCH₂CH═CH₂ CH₂CH═CHCO₂H 546. OCH₂CONH₂ H OCH₂CH═CH₂ CH₂CH═CHCO₂H 547. OCH₂CONH₂ H OCH₂CH═CH₂ CH₂CH₂P— O(OCH₂CH₃)₂ 548. OCH₂CONH₂ H OCH₂CH═CH₂ CH₂CH₂P—O(OH)₂ 549. OH CH₂N(CH₃)₂ OCH₂CH═CH₂ CO₂CH₂CH₃ 550. OH CH₂N(CH₃)₂ OCH₂CH═CH₂ CO₂H 551. OH CH₂N(CH₃)₂ OCH₂CH═CH₂ CH₂CO₂CH₂CH₃ 552. OH CH₂N(CH₃)₂ OCH₂CH═CH₂ CH₂CO₂H 553. OH CH₂N(CH₃)₂ OCH₂CH═CH₂ CH₂CH₂CO₂CH₂CH₃ 554. OH CH₂N(CH₃)₂ OCH₂CH═CH₂ CH₂CH₂CO₂H 555. OH CH₂N(CH₃)₂ OCH₂CH═CH₂ CH₂CH═CHCO₂H 556. OH CH₂N(CH₃)₂ OCH₂CH═CH₂ CH₂CH═CHCO₂H 557. OH CH₂N(CH₃)₂ OCH₂CH═CH₂ CH₂CH₂P— O(OCH₂CH₃)₂ 558. OH CH₂N(CH₃)₂ OCH₂CH═CH₂ CH₂CH₂P—O(OH)₂ 559. OCH₃ CH₂N(CH₃)₂ OCH₂CH═CH₂ CO₂CH₂CH₃ 560. OCH₃ CH₂N(CH₃)₂ OCH₂CH═CH₂ CO₂H 561. OCH₃ CH₂N(CH₃)₂ OCH₂CH═CH₂ CH₂CO₂CH₂CH₃ 562. OCH₃ CH₂N(CH₃)₂ OCH₂CH═CH₂ CH₂CO₂H 563. OCH₃ CH₂N(CH₃)₂ OCH₂CH═CH₂ CH₂CH₂CO₂CH₂CH₃ 564. OCH₃ CH₂N(CH₃)₂ OCH₂CH═CH₂ CH₂CH₂CO₂H 565. OCH₃ CH₂N(CH₃)₂ OCH₂CH═CH₂ CH₂CH═CHCO₂H 566. OCH₃ CH₂N(CH₃)₂ OCH₂CH═CH₂ CH₂CH═CHCO₂H 567. OCH₃ CH₂N(CH₃)₂ OCH₂CH═CH₂ CH₂CH₂P— O(OCH₂CH₃)₂ 568. OCH₃ CH₂N(CH₃)₂ OCH₂CH═CH₂ CH₂CH₂P—O(OH)₂ 569. OH CH₂N⁺(CH₃)₃ OCH₂CH═CH₂ H Cl⁻ 570. OH CH₂N⁺(CH₃)₃ OCH₂CH═CH₂ CH₃ Cl⁻ 571. OH CH₂N⁺(CH₃)₃ OCH₂CH═CH₂ CO₂CH₂CH₃ Cl⁻ 572. OH CH₂N⁺(CH₃)₃ OCH₂CH═CH₂ CO₂H Cl⁻ 573. OH CH₂N⁺(CH₃)₃ OCH₂CH═CH₂ CH₂CO₂CH₂CH₃ Cl⁻ 574. OH CH₂N⁺(CH₃)₃ OCH₂CH═CH₂ CH₂CO₂H Cl⁻ 575. OH CH₂N⁺(CH₃)₃ OCH₂CH═CH₂ CH₂CH₂CO₂CH₂CH₃ Cl⁻ 576. OH CH₂N⁺(CH₃)₃ OCH₂CH═CH₂ CH₂CH₂CO₂H Cl⁻ 577. OH CH₂N⁺(CH₃)₃ OCH₂CH═CH₂ CH₂CH═CHCO₂H Cl⁻ 578. OH CH₂N⁺(CH₃)₃ OCH₂CH═CH₂ CH₂CH═CHCO₂H Cl⁻ 579. OH CH₂N⁺(CH₃)₃ OCH₂CH═CH₂ CH₂CH₂P— Cl⁻ O(OCH₂CH₃)₂ 580. OH CH₂N⁺(CH₃)₃ OCH₂CH═CH₂ CH₂CH₂P—O(OH)₂ Cl⁻ 581. OCH₃ CH₂N⁺(CH₃)₃ OCH₂CH═CH₂ H Cl⁻ 582. OCH₃ CH₂N⁺(CH₃)₃ OCH₂CH═CH₂ CH₃ Cl⁻ 583. OCH₃ CH₂N⁺(CH₃)₃ OCH₂CH═CH₂ CO₂CH₂CH₃ Cl⁻ 584. OCH₃ CH₂N⁺(CH₃)₃ OCH₂CH═CH₂ CO₂H Cl⁻ 585. OCH₃ CH₂N⁺(CH₃)₃ OCH₂CH═CH₂ CH₂CO₂CH₂CH₃ Cl⁻ 586. OCH₃ CH₂N⁺(CH₃)₃ OCH₂CH═CH₂ CH₂CO₂H Cl⁻ 587. OCH₃ CH₂N⁺(CH₃)₃ OCH₂CH═CH₂ CH₂CH₂CO₂CH₂CH₃ Cl⁻ 588. OCH₃ CH₂N⁺(CH₃)₃ OCH₂CH═CH₂ CH₂CH₂CO₂H Cl⁻ 589. OCH₃ CH₂N⁺(CH₃)₃ OCH₂CH═CH₂ CH₂CH═CHCO₂H Cl⁻ 590. OCH₃ CH₂N⁺(CH₃)₃ OCH₂CH═CH₂ CH₂CH═CHCO₂H Cl⁻ 591. OCH₃ CH₂N⁺(CH₃)₃ OCH₂CH═CH₂ CH₂CH₂P— Cl⁻ O(OCH₂CH₃)₂ 592. OCH₃ CH₂N⁺(CH₃)₃ OCH₂CH═CH₂ CH₂CH₂P—O(OH)₂ Cl⁻ 593. H H OCH₂CONH₂ H 594. H H OCH₂CONH₂ CH₃ 595. H H OCH₂CONH₂ CO₂CH₂CH₃ 596. H H OCH₂CONH₂ CO₂H 597. H H OCH₂CONH₂ CH₂CO₂CH₂CH₃ 598. H H OCH₂CONH₂ CH₂CO₂H 599. H H OCH₂CONH₂ CH₂CH₂CO₂CH₂CH₃ 600. H H OCH₂CONH₂ CH₂CH₂CO₂H 601. H H OCH₂CONH₂ CH₂CH═CHCO₂H 602. H H OCH₂CONH₂ CH₂CH═CHCO₂H 603. H H OCH₂CONH₂ CH₂CH₂P— O(OCH₂CH₃)₂ 604. H H OCH₂CONH₂ CH₂CH₂P—O(OH)₂ 605. OH H OCH₂CONH₂ H 606. OH H OCH₂CONH₂ CH₃ 607. OH H OCH₂CONH₂ CO₂CH₂CH₃ 608. OH H OCH₂CONH₂ CO₂H 609. OH H OCH₂CONH₂ CH₂CO₂CH₂CH₃ 610. OH H OCH₂CONH₂ CH₂CO₂H 611. OH H OCH₂CONH₂ CH₂CH₂CO₂CH₂CH₃ 612. OH H OCH₂CONH₂ CH₂CH₂CO₂H 613. OH H OCH₂CONH₂ CH₂CH═CHCO₂H 614. OH H OCH₂CONH₂ CH₂CH═CHCO₂H 615. OH H OCH₂CONH₂ CH₂CH₂P— O(OCH₂CH₃)₂ 616. OH H OCH₂CONH₂ CH₂CH₂P—O(OH)₂ 617. OCH₃ H OCH₂CONH₂ H 618. OCH₃ H OCH₂CONH₂ CH₃ 619. OCH₃ H OCH₂CONH₂ CO₂CH₂CH₃ 620. OCH₃ H OCH₂CONH₂ CO₂H 621. OCH₃ H OCH₂CONH₂ CH₂CO₂CH₂CH₃ 622. OCH₃ H OCH₂CONH₂ CH₂CO₂H 623. OCH₃ H OCH₂CONH₂ CH₂CH₂CO₂CH₂CH₃ 624. OCH₃ H OCH₂CONH₂ CH₂CH₂CO₂H 625. OCH₃ H OCH₂CONH₂ CH₂CH═CHCO₂H 626. OCH₃ H OCH₂CONH₂ CH₂CH═CHCO₂H 627. OCH₃ H OCH₂CONH₂ CH₂CH₂P— O(OCH₂CH₃)₂ 628. OCH₃ H OCH₂CONH₂ CH₂CH₂P—O(OH)₂ 629. OCH₂CH═CH₂ H OCH₂CONH₂ H 630. OCH₂CH═CH₂ H OCH₂CONH₂ CH₃ 631. OCH₂CH═CH₂ H OCH₂CONH₂ CO₂CH₂CH₃ 632. OCH₂CH═CH₂ H OCH₂CONH₂ CO₂H 633. OCH₂CH═CH₂ H OCH₂CONH₂ CH₂CO₂CH₂CH₃ 634. OCH₂CH═CH₂ H OCH₂CONH₂ CH₂CO₂H 635. OCH₂CH═CH₂ H OCH₂CONH₂ CH₂CH₂CO₂CH₂CH₃ 636. OCH₂CH═CH₂ H OCH₂CONH₂ CH₂CH₂CO₂H 637. OCH₂CH═CH₂ H OCH₂CONH₂ CH₂CH═CHCO₂H 638. OCH₂CH═CH₂ H OCH₂CONH₂ CH₂CH═CHCO₂H 639. OCH₂CH═CH₂ H OCH₂CONH₂ CH₂CH₂P— O(OCH₂CH₃)₂ 640. OCH₂CH═CH₂ H OCH₂CONH₂ CH₂CH₂P—O(OH)₂ 641. OCH₂C₆H₅ H OCH₂CONH₂ H 642. OCH₂C₆H₅ H OCH₂CONH₂ CH₃ 643. OCH₂C₆H₅ H OCH₂CONH₂ CO₂CH₂CH₃ 644. OCH₂C₆H₅ H OCH₂CONH₂ CO₂H 645. OCH₂C₆H₅ H OCH₂CONH₂ CH₂CO₂CH₂CH₃ 646. OCH₂C₆H₅ H OCH₂CONH₂ CH₂CO₂H 647. OCH₂C₆H₅ H OCH₂CONH₂ CH₂CH₂CO₂CH₂CH₃ 648. OCH₂C₆H₅ H OCH₂CONH₂ CH₂CH₂CO₂H 649. OCH₂C₆H₅ H OCH₂CONH₂ CH₂CH═CHCO₂H 650. OCH₂C₆H₅ H OCH₂CONH₂ CH₂CH═CHCO₂H 651. OCH₂C₆H₅ H OCH₂CONH₂ CH₂CH₂P— O(OCH₂CH₃)₂ 652. OCH₂C₆H₅ H OCH₂CONH₂ CH₂CH₂P—O(OH)₂ 653. Cl H OCH₂CONH₂ H 654. Cl H OCH₂CONH₂ CH₃ 655. Cl H OCH₂CONH₂ CO₂CH₂CH₃ 656. Cl H OCH₂CONH₂ CO₂H 657. Cl H OCH₂CONH₂ CH₂CO₂CH₂CH₃ 658. Cl H OCH₂CONH₂ CH₂CO₂H 659. Cl H OCH₂CONH₂ CH₂CH₂CO₂CH₂CH₃ 660. Cl H OCH₂CONH₂ CH₂CH₂CO₂H 661. Cl H OCH₂CONH₂ CH₂CH═CHCO₂H 662. Cl H OCH₂CONH₂ CH₂CH═CHCO₂H 663. Cl H OCH₂CONH₂ CH₂CH₂P— O(OCH₂CH₃)₂ 664. Cl H OCH₂CONH₂ CH₂CH₂P—O(OH)₂ 665. NO₂ H OCH₂CONH₂ H 666. NO₂ H OCH₂CONH₂ CH₃ 667. NO₂ H OCH₂CONH₂ CO₂CH₂CH₃ 668. NO₂ H OCH₂CONH₂ CO₂H 669. NO₂ H OCH₂CONH₂ CH₂CO₂CH₂CH₃ 670. NO₂ H OCH₂CONH₂ CH₂CO₂H 671. NO₂ H OCH₂CONH₂ CH₂CH₂CO₂CH₂CH₃ 672. NO₂ H OCH₂CONH₂ CH₂CH₂CO₂H 673. NO₂ H OCH₂CONH₂ CH₂CH═CHCO₂H 674. NO₂ H OCH₂CONH₂ CH₂CH═CHCO₂H 675. NO₂ H OCH₂CONH₂ CH₂CH₂P— O(OCH₂CH₃)₂ 676. NO₂ H OCH₂CONH₂ CH₂CH₂P—O(OH)₂ 677. NH₂ H OCH₂CONH₂ H 678. NH₂ H OCH₂CONH₂ CH₃ 679. NH₂ H OCH₂CONH₂ CO₂CH₂CH₃ 680. NH₂ H OCH₂CONH₂ CO₂H 681. NH₂ H OCH₂CONH₂ CH₂CO₂CH₂CH₃ 682. NH₂ H OCH₂CONH₂ CH₂CO₂H 683. NH₂ H OCH₂CONH₂ CH₂CH₂CO₂CH₂CH₃ 684. NH₂ H OCH₂CONH₂ CH₂CH₂CO₂H 685. NH₂ H OCH₂CONH₂ CH₂CH═CHCO₂H 686. NH₂ H OCH₂CONH₂ CH₂CH═CHCO₂H 687. NH₂ H OCH₂CONH₂ CH₂CH₂P— O(OCH₂CH₃)₂ 688. NH₂ H OCH₂CONH₂ CH₂CH₂P—O(OH)₂ 689. NHSO₂CH₃ H OCH₂CONH₂ H 690. NHSO₂CH₃ H OCH₂CONH₂ CH₃ 691. NHSO₂CH₃ H OCH₂CONH₂ CO₂CH₂CH₃ 692. NHSO₂CH₃ H OCH₂CONH₂ CO₂H 693. NHSO₂CH₃ H OCH₂CONH₂ CH₂CO₂CH₂CH₃ 694. NHSO₂CH₃ H OCH₂CONH₂ CH₂CO₂H 695. NHSO₂CH₃ H OCH₂CONH₂ CH₂CH₂CO₂CH₂CH₃ 696. NHSO₂CH₃ H OCH₂CONH₂ CH₂CH₂CO₂H 697. NHSO₂CH₃ H OCH₂CONH₂ CH₂CH═CHCO₂H 698. NHSO₂CH₃ H OCH₂CONH₂ CH₂CH═CHCO₂H 699. NHSO₂CH₃ H OCH₂CONH₂ CH₂CH₂P— O(OCH₂CH₃)₂ 700. NHSO₂CH₃ H OCH₂CONH₂ CH₂CH₂P—O(OH)₂ 701. OCH₂CONH₂ H OCH₂CONH₂ H 702. OCH₂CONH₂ H OCH₂CONH₂ CH₃ 703. OCH₂CONH₂ H OCH₂CONH₂ CO₂CH₂CH₃ 704. OCH₂CONH₂ H OCH₂CONH₂ CO₂H 705. OCH₂CONH₂ H OCH₂CONH₂ CH₂CO₂CH₂CH₃ 706. OCH₂CONH₂ H OCH₂CONH₂ CH₂CO₂H 707. OCH₂CONH₂ H OCH₂CONH₂ CH₂CH₂CO₂CH₂CH₃ 708. OCH₂CONH₂ H OCH₂CONH₂ CH₂CH₂CO₂H 709. OCH₂CONH₂ H OCH₂CONH₂ CH₂CH═CHCO₂H 710. OCH₂CONH₂ H OCH₂CONH₂ CH₂CH═CHCO₂H 711. OCH₂CONH₂ H OCH₂CONH₂ CH₂CH₂P— O(OCH₂CH₃)₂ 712. OCH₂CONH₂ H OCH₂CONH₂ CH₂CH₂P—O(OH)₂ 713. OH CH₂N(CH₃)₂ OCH₂CONH₂ H 714. OH CH₂N(CH₃)₂ OCH₂CONH₂ CH₃ 715. OH CH₂N(CH₃)₂ OCH₂CONH₂ CO₂CH₂CH₃ 716. OH CH₂N(CH₃)₂ OCH₂CONH₂ CO₂H 717. OH CH₂N(CH₃)₂ OCH₂CONH₂ CH₂CO₂CH₂CH₃ 718. OH CH₂N(CH₃)₂ OCH₂CONH₂ CH₂CO₂H 719. OH CH₂N(CH₃)₂ OCH₂CONH₂ CH₂CH₂CO₂CH₂CH₃ 720. OH CH₂N(CH₃)₂ OCH₂CONH₂ CH₂CH₂CO₂H 721. OH CH₂N(CH₃)₂ OCH₂CONH₂ CH₂CH═CHCO₂H 722. OH CH₂N(CH₃)₂ OCH₂CONH₂ CH₂CH═CHCO₂H 723. OH CH₂N(CH₃)₂ OCH₂CONH₂ CH₂CH₂P— O(OCH₂CH₃)₂ 724. OH CH₂N(CH₃)₂ OCH₂CONH₂ CH₂CH₂P—O(OH)₂ 725. OCH₃ CH₂N(CH₃)₂ OCH₂CONH₂ H 726. OCH₃ CH₂N(CH₃)₂ OCH₂CONH₂ CH₃ 727. OCH₃ CH₂N(CH₃)₂ OCH₂CONH₂ CO₂CH₂CH₃ 728. OCH₃ CH₂N(CH₃)₂ OCH₂CONH₂ CO₂H 729. OCH₃ CH₂N(CH₃)₂ OCH₂CONH₂ CH₂CO₂CH₂CH₃ 730. OCH₃ CH₂N(CH₃)₂ OCH₂CONH₂ CH₂CO₂H 731. OCH₃ CH₂N(CH₃)₂ OCH₂CONH₂ CH₂CH₂CO₂CH₂CH₃ 732. OCH₃ CH₂N(CH₃)₂ OCH₂CONH₂ CH₂CH₂CO₂H 733. OCH₃ CH₂N(CH₃)₂ OCH₂CONH₂ CH₂CH═CHCO₂H 734. OCH₃ CH₂N(CH₃)₂ OCH₂CONH₂ CH₂CH═CHCO₂H 735. OCH₃ CH₂N(CH₃)₂ OCH₂CONH₂ CH₂CH₂P— O(OCH₂CH₃)₂ 736. OCH₃ CH₂N(CH₃)₂ OCH₂CONH₂ CH₂CH₂P—O(OH)₂ 737. OH CH₂N⁺(CH₃)₃ OCH₂CONH₂ H Cl⁻ 738. OH CH₂N⁺(CH₃)₃ OCH₂CONH₂ CH₃ Cl⁻ 739. OH CH₂N⁺(CH₃)₃ OCH₂CONH₂ CO₂CH₂CH₃ Cl⁻ 740. OH CH₂N⁺(CH₃)₃ OCH₂CONH₂ CO₂H Cl⁻ 741. OH CH₂N⁺(CH₃)₃ OCH₂CONH₂ CH₂CO₂CH₂CH₃ Cl⁻ 742. OH CH₂N⁺(CH₃)₃ OCH₂CONH₂ CH₂CO₂H Cl⁻ 743. OH CH₂N⁺(CH₃)₃ OCH₂CONH₂ CH₂CH₂CO₂CH₂CH₃ Cl⁻ 744. OH CH₂N⁺(CH₃)₃ OCH₂CONH₂ CH₂CH₂CO₂H Cl⁻ 745. OH CH₂N⁺(CH₃)₃ OCH₂CONH₂ CH₂CH═CHCO₂H Cl⁻ 746. OH CH₂N⁺(CH₃)₃ OCH₂CONH₂ CH₂CH═CHCO₂H Cl⁻ 747. OH CH₂N⁺(CH₃)₃ OCH₂CONH₂ CH₂CH₂P— Cl⁻ O(OCH₂CH₃)₂ 748. OH CH₂N⁺(CH₃)₃ OCH₂CONH₂ CH₂CH₂P—O(OH)₂ Cl⁻ 749. OCH₃ CH₂N⁺(CH₃)₃ OCH₂CONH₂ H Cl⁻ 750. OCH₃ CH₂N⁺(CH₃)₃ OCH₂CONH₂ CH₃ Cl⁻ 751. OCH₃ CH₂N⁺(CH₃)₃ OCH₂CONH₂ CO₂CH₂CH₃ Cl⁻ 752. OCH₃ CH₂N⁺(CH₃)₃ OCH₂CONH₂ CO₂H Cl⁻ 753. OCH₃ CH₂N⁺(CH₃)₃ OCH₂CONH₂ CH₂CO₂CH₂CH₃ Cl⁻ 754. OCH₃ CH₂N⁺(CH₃)₃ OCH₂CONH₂ CH₂CO₂H Cl⁻ 755. OCH₃ CH₂N⁺(CH₃)₃ OCH₂CONH₂ CH₂CH₂CO₂CH₂CH₃ Cl⁻ 756. OCH₃ CH₂N⁺(CH₃)₃ OCH₂CONH₂ CH₂CH₂CO₂H Cl⁻ 757. OCH₃ CH₂N⁺(CH₃)₃ OCH₂CONH₂ CH₂CH═CHCO₂H Cl⁻ 758. OCH₃ CH₂N⁺(CH₃)₃ OCH₂CONH₂ CH₂CH═CHCO₂H Cl⁻ 759. OCH₃ CH₂N⁺(CH₃)₃ OCH₂CONH₂ CH₂CH₂P— Cl⁻ O(OCH₂CH₃)₂ 760. OCH₃ CH₂N⁺(CH₃)₃ OCH₂CONH₂ CH₂CH₂P—O(OH)₂ Cl⁻ 761. H H H CH₂-tetrazole 762. OCH₃ H H CH₂-tetrazole 763. OCH₂C₆H₅ H H CH₂-tetrazole

TABLE VI

Cl is present when Q is other than O. Ex. # X Q R¹ 1. H CH₃ H 2. H CH₂CH═CH₂ H 3. H CH₂C≡CH H 4. H O⁻ H 5. H CH₃ CH₃ 6. H CH₂CH═CH₂ CH₃ 7. H CH₂C≡CH CH₃ 8. H O⁻ CH₃ 9. H CH₃ CH₂CO₂CH₂CH₃ 10. H CH₂CH═CH₂ CH₂CO₂CH₂CH₃ 11. H CH₂C≡CH CH₂CO₂CH₂CH₃ 12. H O⁻ CH₂CO₂CH₂CH₃ 13. H CH₃ CH₂CH₂PO(OCH₂CH₃)₂ 14. H CH₂CH═CH₂ CH₂CH₂PO(OCH₂CH₃)₂ 15. H CH₂C≡CH CH₂CH₂PO(OCH₂CH₃)₂ 16. H O⁻ CH₂CH₂PO(OCH₂CH₃)₂ 17. OH CH₃ H 18. OH CH₂CH═CH₂ H 19. OH CH₂C≡CH H 20. OH O⁻ H 21. OH CH₃ CH₃ 22. OH CH₂CH═CH₂ CH₃ 23. OH CH₂C≡CH CH₃ 24. OH O⁻ CH₃ 25. OH CH₃ CH₂CO₂CH₂CH₃ 26. OH CH₂CH═CH₂ CH₂CO₂CH₂CH₃ 27. OH CH₂C≡CH CH₂CO₂CH₂CH₃ 28. OH O⁻ CH₂CO₂CH₂CH₃ 29. OH CH₃ CH₂CH₂PO(OCH₂CH₃)₂ 30. OH CH₂CH═CH₂ CH₂CH₂PO(OCH₂CH₃)₂ 31. OH CH₂C≡CH CH₂CH₂PO(OCH₂CH₃)₂ 32. OH O⁻ CH₂CH₂PO(OCH₂CH₃)₂ 33. OCH₃ CH₃ H 34. OCH₃ CH₂CH═CH₂ H 35. OCH₃ CH₂C≡CH H 36. OCH₃ O⁻ H 37. OCH₃ CH₃ CH₃ 38. OCH₃ CH₂CH═CH₂ CH₃ 39. OCH₃ CH₂C≡CH CH₃ 40. OCH₃ O⁻ CH₃ 41. OCH₃ CH₃ CH₂CO₂CH₂CH₃ 42. OCH₃ CH₂CH═CH₂ CH₂CO₂CH₂CH₃ 43. OCH₃ CH₂C≡CH CH₂CO₂CH₂CH₃ 44. OCH₃ O⁻ CH₂CO₂CH₂CH₃ 45. OCH₃ CH₃ CH₂CH₂PO(OCH₂CH₃)₂ 46. OCH₃ CH₂CH═CH₂ CH₂CH₂PO(OCH₂CH₃)₂ 47. OCH₃ CH₂C≡CH CH₂CH₂PO(OCH₂CH₃)₂ 48. OCH₃ O⁻ CH₂CH₂PO(OCH₂CH₃)₂ 49. Cl CH₃ H 50. Cl CH₂CH═CH₂ H 51. Cl CH₂C≡CH H 52. Cl O⁻ H 53. Cl CH₃ CH₃ 54. Cl CH₂CH═CH₂ CH₃ 55. Cl CH₂C≡CH CH₃ 56. Cl O⁻ CH₃ 57. Cl CH₃ CH₂CO₂CH₂CH₃ 58. Cl CH₂CH═CH₂ CH₂CO₂CH₂CH₃ 59. Cl CH₂C≡CH CH₂CO₂CH₂CH₃ 60. Cl O⁻ CH₂CO₂CH₂CH₃ 61. Cl CH₃ CH₂CH₂PO(OCH₂CH₃)₂ 62. Cl CH₂CH═CH₂ CH₂CH₂PO(OCH₂CH₃)₂ 63. Cl CH₂C≡CH CH₂CH₂PO(OCH₂CH₃)₂ 64. Cl O⁻ CH₂CH₂PO(OCH₂CH₃)₂ 65. NO₂ CH₃ H 66. NO₂ CH₂CH═CH₂ H 67. NO₂ CH₂C≡CH H 68. NO₂ O⁻ H 69. NO₂ CH₃ CH₃ 70. NO₂ CH₂CH═CH₂ CH₃ 71. NO₂ CH₂C≡CH CH₃ 72. NO₂ O⁻ CH₃ 73. NO₂ CH₃ CH₂CO₂CH₂CH₃ 74. NO₂ CH₂CH═CH₂ CH₂CO₂CH₂CH₃ 75. NO₂ CH₂C≡CH CH₂CO₂CH₂CH₃ 76. NO₂ O⁻ CH₂CO₂CH₂CH₃ 77. NO₂ CH₃ CH₂CH₂PO(OCH₂CH₃)₂ 78. NO₂ CH₂CH═CH₂ CH₂CH₂PO(OCH₂CH₃)₂ 79. NO₂ CH₂C≡CH CH₂CH₂PO(OCH₂CH₃)₂ 80. NO₂ O⁻ CH₂CH₂PO(OCH₂CH₃)₂ 81. NH₂ CH₃ H 82. NH₂ CH₂CH═CH₂ H 83. NH₂ CH₂C≡CH H 84. NH₂ O⁻ H 85. NH₂ CH₃ CH₃ 86. NH₂ CH₂CH═CH₂ CH₃ 87. NH₂ CH₂C≡CH CH₃ 88. NH₂ O⁻ CH₃ 89. NH₂ CH₃ CH₂CO₂CH₂CH₃ 90. NH₂ CH₂CH═CH₂ CH₂CO₂CH₂CH₃ 91. NH₂ CH₂C≡CH CH₂CO₂CH₂CH₃ 92. NH₂ O⁻ CH₂CO₂CH₂CH₃ 93. NH₂ CH₃ CH₂CH₂PO(OCH₂CH₃)₂ 94. NH₂ CH₂CH═CH₂ CH₂CH₂PO(OCH₂CH₃)₂ 95. NH₂ CH₂C≡CH CH₂CH₂PO(OCH₂CH₃)₂ 96. NH₂ O⁻ CH₂CH₂PO(OCH₂CH₃)₂ 97. NHSO₂CH₃ CH₃ H 98. NHSO₂CH₃ CH₂CH═CH₂ H 99. NHSO₂CH₃ CH₂C≡CH H 100. NHSO₂CH₃ O⁻ H 101. NHSO₂CH₃ CH₃ CH₃ 102. NHSO₂CH₃ CH₂CH═CH₂ CH₃ 103. NHSO₂CH₃ CH₂C≡CH CH₃ 104. NHSO₂CH₃ O⁻ CH₃ 105. NHSO₂CH₃ CH₃ CH₂CO₂CH₂CH₃ 106. NHSO₂CH₃ CH₂CH═CH₂ CH₂CO₂CH₂CH₃ 107. NHSO₂CH₃ CH₂C≡CH CH₂CO₂CH₂CH₃ 108. NHSO₂CH₃ O⁻ CH₂CO₂CH₂CH₃ 109. NHSO₂CH₃ CH₃ CH₂CH₂PO(OCH₂CH₃)₂ 110. NHSO₂CH₃ CH₂CH═CH₂ CH₂CH₂PO(OCH₂CH₃)₂ 111. NHSO₂CH₃ CH₂C≡CH CH₂CH₂PO(OCH₂CH₃)₂ 112. NHSO₂CH₃ O⁻ CH₂CH₂PO(OCH₂CH₃)₂ 113. OCH₂C₆H₅ CH₃ H 114. OCH₂C₆H₅ CH₂CH═CH₂ H 115. OCH₂C₆H₅ CH₂C≡CH H 116. OCH₂C₆H₅ O⁻ H 117. OCH₂C₆H₅ CH₃ CH₃ 118. OCH₂C₆H₅ CH₂CH═CH₂ CH₃ 119. OCH₂C₆H₅ CH₂C≡CH CH₃ 120. OCH₂C₆H₅ O⁻ CH₃ 121. OCH₂C₆H₅ CH₃ CH₂CO₂CH₂CH₃ 122. OCH₂C₆H₅ CH₂CH═CH₂ CH₂CO₂CH₂CH₃ 123. OCH₂C₆H₅ CH₂C≡CH CH₂CO₂CH₂CH₃ 124. OCH₂C₆H₅ O⁻ CH₂CO₂CH₂CH₃ 125. OCH₂C₆H₅ CH₃ CH₂CH₂PO(OCH₂CH₃)₂ 126. OCH₂C₆H₅ CH₂CH═CH₂ CH₂CH₂PO(OCH₂CH₃)₂ 127. OCH₂C₆H₅ CH₂C≡CH CH₂CH₂PO(OCH₂CH₃)₂ 128. OCH₂C₆H₅ O⁻ CH₂CH₂PO(OCH₂CH₃)₂ 129. OCH₂CH₂C₆H₅ CH₃ H 130. OCH₂CH₂C₆H₅ CH₂CH═CH₂ H 131. OCH₂CH₂C₆H₅ CH₂C≡CH H 132. OCH₂CH₂C₆H₅ O⁻ H 133. OCH₂CH₂C₆H₅ CH₃ CH₃ 134. OCH₂CH₂C₆H₅ CH₂CH═CH₂ CH₃ 135. OCH₂CH₂C₆H₅ CH₂C≡CH CH₃ 136. OCH₂CH₂C₆H₅ O⁻ CH₃ 137. OCH₂C₆H₄—Cl CH₃ H 2, 3, or 4 138. OCH₂C₆H₄—Cl CH₂CH═CH₂ H 2, 3, or 4 139. OCH₂C₆H₄—Cl CH₂CCH H 2, 3, or 4 140. OCH₂C₆H₄—Cl O⁻ H 2, 3, or 4 141. OCH₂C₆H₄—Cl CH₃ CH₃ 2, 3, or 4 142. OCH₂C₆H₄—Cl CH₂CH═CH₂ CH₃ 2, 3, or 4 143. OCH₂C₆H₄—Cl CH₂C≡CH CH₃ 2, 3, or 4 144. OCH₂C₆H₄—Cl O⁻ CH₃ 2, 3, or 4 145. OCH₂C₆H₄OCH₃ CH₃ H 2, 3, or 4 146. OCH₂C₆H₄OCH₃ CH₂CH═CH₂ H 2, 3, or 4 147. OCH₂C₆H₄OCH₃ CH₂C≡CH H 2, 3, or 4 148. OCH₂C₆H₄OCH₃ O⁻ H 2, 3, or 4 149. OCH₂C₆H₄OCH₃ CH₃ CH₃ 2, 3, or 4 150. OCH₂C₆H₄OCH₃ CH₂CH═CH₂ CH₃ (2, 3, or 4) 151. OCH₂C₆H₄OCH₃ CH₂C≡CH CH₃ 2, 3, or 4 152. OCH₂C₆H₄OCH₃ O⁻ CH₃ 2, 3, or 4 153. OCH₂C₆H₄C₆H₅ CH₃ H 154. OCH₂C₆H₄C₆H₅ CH₂CH═CH₂ H 155. OCH₂C₆H₄C₆H₅ CH₂C≡CH H 156. OCH₂C₆H₄C₆H₅ O⁻ H 157. OCH₂C₆H₄C₆H₅ CH₃ CH₃ 158. OCH₂C₆H₄C₆H₅ CH₂CH═CH₂ CH₃ 159. OCH₂C₆H₄C₆H₅ CH₂C≡CH CH₃ 160. OCH₂C₆H₄C₆H₅ O⁻ CH₃

TABLE VII

Cl is present when Q is other than O. Ex. # X Q R¹ 1. H CH₃ H 2. H CH₂CH═CH₂ H 3. H CH₂C≡CH H 4. H O⁻ H 5. H CH₃ CH₃ 6. H CH₂CH═CH₂ CH₃ 7. H CH₂C≡CH CH₃ 8. H O⁻ CH₃ 9. H CH₃ CH₂CO₂CH₂CH₃ 10. H CH₂CH═CH₂ CH₂CO₂CH₂CH₃ 11. H CH₂C≡CH CH₂CO₂CH₂CH₃ 12. H O⁻ CH₂CO₂CH₂CH₃ 13. H CH₃ CH₂CH₂PO(OCH₂CH₃)₂ 14. H CH₂CH═CH₂ CH₂CH₂PO(OCH₂CH₃)₂ 15. H CH₂C≡CH CH₂CH₂PO(OCH₂CH₃)₂ 16. H O⁻ CH₂CH₂PO(OCH₂CH₃)₂ 17. OH CH₃ H 18. OH CH₂CH═CH₂ H 19. OH CH₂C≡CH H 20. OH O⁻ H 21. OH CH₃ CH₃ 22. OH CH₂CH═CH₂ CH₃ 23. OH CH₂C≡CH CH₃ 24. OH O⁻ CH₃ 25. OH CH₃ CH₂CO₂CH₂CH₃ 26. OH CH₂CH═CH₂ CH₂CO₂CH₂CH₃ 27. OH CH₂C≡CH CH₂CO₂CH₂CH₃ 28. OH O⁻ CH₂CO₂CH₂CH₃ 29. OH CH₃ CH₂CH₂PO(OCH₂CH₃)₂ 30. OH CH₂CH═CH₂ CH₂CH₂PO(OCH₂CH₃)₂ 31. OH CH₂C≡CH CH₂CH₂PO(OCH₂CH₃)₂ 32. OH O⁻ CH₂CH₂PO(OCH₂CH₃)₂ 33. OCH₃ CH₃ H 34. OCH₃ CH₂CH═CH₂ H 35. OCH₃ CH₂C≡CH H 36. OCH₃ O⁻ H 37. OCH₃ CH₃ CH₃ 38. OCH₃ CH₂CH═CH₂ CH₃ 39. OCH₃ CH₂C≡CH CH₃ 40. OCH₃ O⁻ CH₃ 41. OCH₃ CH₃ CH₂CO₂CH₂CH₃ 42. OCH₃ CH₂CH═CH₂ CH₂CO₂CH₂CH₃ 43. OCH₃ CH₂C≡CH CH₂CO₂CH₂CH₃ 44. OCH₃ O⁻ CH₂CO₂CH₂CH₃ 45. OCH₃ CH₃ CH₂CH₂PO(OCH₂CH₃)₂ 46. OCH₃ CH₂CH═CH₂ CH₂CH₂PO(OCH₂CH₃)₂ 47. OCH₃ CH₂C≡CH CH₂CH₂PO(OCH₂CH₃)₂ 48. OCH₃ O⁻ CH₂CH₂PO(OCH₂CH₃)₂ 49. Cl CH₃ H 50. Cl CH₂CH═CH₂ H 51. Cl CH₂C≡CH H 52. Cl O⁻ H 53. Cl CH₃ CH₃ 54. Cl CH₂CH═CH₂ CH₃ 55. Cl CH₂C≡CH CH₃ 56. Cl O⁻ CH₃ 57. Cl CH₃ CH₂CO₂CH₂CH₃ 58. Cl CH₂CH═CH₂ CH₂CO₂CH₂CH₃ 59. Cl CH₂C≡CH CH₂CO₂CH₂CH₃ 60. Cl O⁻ CH₂CO₂CH₂CH₃ 61. Cl CH₃ CH₂CH₂PO(OCH₂CH₃)₂ 62. Cl CH₂CH═CH₂ CH₂CH₂PO(OCH₂CH₃)₂ 63. Cl CH₂C≡CH CH₂CH₂PO(OCH₂CH₃)₂ 64. Cl O⁻ CH₂CH₂PO(OCH₂CH₃)₂ 65. NO₂ CH₃ H 66. NO₂ CH₂CH═CH₂ H 67. NO₂ CH₂C≡CH H 68. NO₂ O⁻ H 69. NO₂ CH₃ CH₃ 70. NO₂ CH₂CH═CH₂ CH₃ 71. NO₂ CH₂C≡CH CH₃ 72. NO₂ O⁻ CH₃ 73. NO₂ CH₃ CH₂CO₂CH₂CH₃ 74. NO₂ CH₂CH═CH₂ CH₂CO₂CH₂CH₃ 75. NO₂ CH₂C≡CH CH₂CO₂CH₂CH₃ 76. NO₂ O⁻ CH₂CO₂CH₂CH₃ 77. NO₂ CH₃ CH₂CH₂PO(OCH₂CH₃)₂ 78. NO₂ CH₂CH═CH₂ CH₂CH₂PO(OCH₂CH₃)₂ 79. NO₂ CH₂C≡CH CH₂CH₂PO(OCH₂CH₃)₂ 80. NO₂ O⁻ CH₂CH₂PO(OCH₂CH₃)₂ 81. NH₂ CH₃ H 82. NH₂ CH₂CH═CH₂ H 83. NH₂ CH₂C≡CH H 84. NH₂ O⁻ H 85. NH₂ CH₃ CH₃ 86. NH₂ CH₂CH═CH₂ CH₃ 87. NH₂ CH₂C≡CH CH₃ 88. NH₂ O⁻ CH₃ 89. NH₂ CH₃ CH₂CO₂CH₂CH₃ 90. NH₂ CH₂CH═CH₂ CH₂CO₂CH₂CH₃ 91. NH₂ CH₂C≡CH CH₂CO₂CH₂CH₃ 92. NH₂ O⁻ CH₂CO₂CH₂CH₃ 93. NH₂ CH₃ CH₂CH₂PO(OCH₂CH₃)₂ 94. NH₂ CH₂CH═CH₂ CH₂CH₂PO(OCH₂CH₃)₂ 95. NH₂ CH₂C≡CH CH₂CH₂PO(OCH₂CH₃)₂ 96. NH₂ O⁻ CH₂CH₂PO(OCH₂CH₃)₂ 97. NHSO₂CH₃ CH₃ H 98. NHSO₂CH₃ CH₂CH═CH₂ H 99. NHSO₂CH₃ CH₂C≡CH H 100. NHSO₂CH₃ O⁻ H 101. NHSO₂CH₃ CH₃ CH₃ 102. NHSO₂CH₃ CH₂CH═CH₂ CH₃ 103. NHSO₂CH₃ CH₂C≡CH CH₃ 104. NHSO₂CH₃ O⁻ CH₃ 105. NHSO₂CH₃ CH₃ CH₂CO₂CH₂CH₃ 106. NHSO₂CH₃ CH₂CH═CH₂ CH₂CO₂CH₂CH₃ 107. NHSO₂CH₃ CH₂C≡CH CH₂CO₂CH₂CH₃ 108. NHSO₂CH₃ O⁻ CH₂CO₂CH₂CH₃ 109. NHSO₂CH₃ CH₃ CH₂CH₂PO(OCH₂CH₃)₂ 110. NHSO₂CH₃ CH₂CH═CH₂ CH₂CH₂PO(OCH₂CH₃)₂ 111. NHSO₂CH₃ CH₂C≡CH CH₂CH₂PO(OCH₂CH₃)₂ 112. NHSO₂CH₃ O⁻ CH₂CH₂PO(OCH₂CH₃)₂ 113. OCH₂C₆H₅ CH₃ H 114. OCH₂C₆H₅ CH₂CH═CH₂ H 115. OCH₂C₆H₅ CH₂C≡CH H 116. OCH₂C₆H₅ O⁻ H 117. OCH₂C₆H₅ CH₃ CH₃ 118. OCH₂C₆H₅ CH₂CH═CH₂ CH₃ 119. OCH₂C₆H₅ CH₂C≡CH CH₃ 120. OCH₂C₆H₅ O⁻ CH₃ 121. OCH₂C₆H₅ CH₃ CH₂CO₂CH₂CH₃ 122. OCH₂C₆H₅ CH₂CH═CH₂ CH₂CO₂CH₂CH₃ 123. OCH₂C₆H₅ CH₂C≡CH CH₂CO₂CH₂CH₃ 124. OCH₂C₆H₅ O⁻ CH₂CO₂CH₂CH₃ 125. OCH₂C₆H₅ CH₃ CH₂CH₂PO(OCH₂CH₃)₂ 126. OCH₂C₆H₅ CH₂CH═CH₂ CH₂CH₂PO(OCH₂CH₃)₂ 127. OCH₂C₆H₅ CH₂C≡CH CH₂CH₂PO(OCH₂CH₃)₂ 128. OCH₂C₆H₅ O⁻ CH₂CH₂PO(OCH₂CH₃)₂ 129. OCH₂CH₂C₆H₅ CH₃ H 130. OCH₂CH₂C₆H₅ CH₂CH═CH₂ H 131. OCH₂CH₂C₆H₅ CH₂C≡CH H 132. OCH₂CH₂C₆H₅ O⁻ H 133. OCH₂CH₂C₆H₅ CH₃ CH₃ 134. OCH₂CH₂C₆H₅ CH₂CH═CH₂ CH₃ 135. OCH₂CH₂C₆H₅ CH₂C≡CH CH₃ 136. OCH₂CH₂C₆H₅ O⁻ CH₃ 137. OCH₂C₆H₄—2-Cl CH₃ H 138. OCH₂C₆H₄—3-Cl CH₃ H 139. OCH₂C₆H₄—4-Cl CH₃ H 140. OCH₂C₆H₄—2-Cl CH₂CH═CH₂ H 141. OCH₂C₆H₄—3-Cl CH₂CH═CH₂ H 142. OCH₂C₆H₄—4-Cl CH₂CH═CH₂ H 143. OCH₂C₆H₄—2-Cl CH₂C≡CH H 144. OCH₂C₆H₄—3-Cl CH₂C≡CH H 145. OCH₂C₆H₄—4-Cl CH₂C≡CH H 146. OCH₂C₆H₄—2-Cl O⁻ H 147. OCH₂C₆H₄—3-Cl O⁻ H 148. OCH₂C₆H₄—4-Cl O⁻ H 149. OCH₂C₆H₄—2-Cl CH₃ CH₃ 150. OCH₂C₆H₄—3-Cl CH₃ CH₃ 151. OCH₂C₆H₄—4-Cl CH₃ CH₃ 152. OCH₂C₆H₄—2-Cl CH₂CH═CH₂ CH₃ 153. OCH₂C₆H₄—3-Cl CH₂CH═CH₂ CH₃ 154. OCH₂C₆H₄—4-Cl CH₂CH═CH₂ CH₃ 155. OCH₂C₆H₄—2-Cl CH₂C≡CH CH₃ 156. OCH₂C₆H₄—3-Cl CH₂C≡CH CH₃ 157. OCH₂C₆H₄—4-Cl CH₂C≡CH CH₃ 158. OCH₂C₆H₄—2-Cl O⁻ CH₃ 159. OCH₂C₆H₄—3-Cl O⁻ CH₃ 160. OCH₂C₆H₄—4-Cl O⁻ CH₃ 161. OCH₂C₆H₄—2- CH₃ H OCH₃ 162. OCH₂C₆H₄—3- CH₃ H OCH₃ 163. OCH₂C₆H₄—4- CH₃ H OCH₃ 164. OCH₂C₆H₄—2- CH₂CH═CH₂ H OCH₃ 165. OCH₂C₆H₄—3- CH₂CH═CH₂ H OCH₃ 166. OCH₂C₆H₄—4- CH₂CH═CH₂ H OCH₃ 167. OCH₂C₆H₄—2- CH₂C≡CH H OCH₃ 168. OCH₂C₆H₄—3- CH₂C≡CH H OCH₃ 169. OCH₂C₆H₄—4- CH₂C≡CH H OCH₃ 170. OCH₂C₆H₄—2- O⁻ H OCH₃ 171. OCH₂C₆H₄—3- O⁻ H OCH₃ 172. OCH₂C₆H₄—4- O⁻ H OCH₃ 173. OCH₂C₆H₄—2- CH₃ CH₃ OCH₃ 174. OCH₂C₆H₄—3- CH₃ CH₃ OCH₃ 175. OCH₂C₆H₄—4- CH₃ CH₃ OCH₃ 176. OCH₂C₆H₄—2- CH₂CH═CH₂ CH₃ OCH₃ 177. OCH₂C₆H₄—3- CH₂CH═CH₂ CH₃ OCH₃ 178. OCH₂C₆H₄—4- CH₂CH═CH₂ CH₃ OCH₃ 179. OCH₂C₆H₄—2- CH₂C≡CH CH₃ OCH₃ 180. OCH₂C₆H₄—3- CH₂C≡CH CH₃ OCH₃ 181. OCH₂C₆H₄—4- CH₂C≡CH CH₃ OCH₃ 182. OCH₂C₆H₄—2- O⁻ CH₃ OCH₃ 183. OCH₂C₆H₄—3- O⁻ CH₃ OCH₃ 184. OCH₂C₆H₄—4- O⁻ CH₃ OCH₃ 185. OCH₂C₆H₄C₆H₅ CH₃ H 186. OCH₂C₆H₄C₆H₅ CH₂CH═CH₂ H 187. OCH₂C₆H₄C₆H₅ CH₂C≡CH H 188. OCH₂C₆H₄C₆H₅ O⁻ H 189. OCH₂C₆H₄C₆H₅ CH₃ CH₃ 190. OCH₂C₆H₄C₆H₅ CH₂CH═CH₂ CH₃ 191. OCH₂C₆H₄C₆H₅ CH₂C≡CH CH₃ 192. OCH₂C₆H₄C₆H₅ O⁻ CH₃

TABLE VIIIa

Ex. # X R¹ 1. NO₂ H 2. NO₂ CH₃ 3. CN H 4. CN CH₃ 5. CONH₂ H 6. CONH₂ CH₃ 7. CO₂H H 8. CO₂H CH₃ 9. NHSO₂CH₃ H 10. NHSO₂CH₃ CH₃ 11. OCH₂C₆H₅ H 12. OCH₂C₆H₅ CH₃ 13. OCH₂C₆H₄C₆H₅ H 14. OCH₂C₆H₄C₆H₅ CH₃ 15. OCH₂CH₂C₆H₅ H 16. OCH₂CH₂C₆H₅ CH₃ 17. OCH₂C₆H₄Cl(2, 3, or 4) H 18. OCH₂C₆H₄Cl(2, 3, or 4) CH₃ 19. OCH₂C₆H₄OCH₃(2, 3, or 4) H 20. OCH₂C₆H₄OCH₃(2, 3, or 4) CH₃ 21. OCH₂C₆H₄F(2, 3, or 4) H 22. OCH₂C₆H₄F(2, 3, or 4) CH₃ 23. OCH₂C₆H₄CN(2, 3, or 4) H 24. OCH₂C₆H₄CN(2, 3, or 4) CH₃ 25. OCH₂C₆H₄CONH₂(2, 3, or 4) H 26. OCH₂C₆H₄CONH₂(2, 3, or 4) CH₃ 27. OCH₂C₆H₄CH₂CN(2, 3, or 4) H 28. OCH₂C₆H₄CH₂CN(2, 3, or 4) CH₃ 29. OCH₂C₆H₄CH₂CONH₂(2, 3, or 4) H 30. OCH₂C₆H₄CH₂CONH₂(2, 3, or 4) CH₃ 31. OCH₂C₆H₄OCH₂CN(2, 3, or 4) H 32. OCH₂C₆H₄OCH₂CN(2, 3, or 4) CH₃ 33. OCH₂C₆H₄OCH₂CONH₂(2, 3, or 4) H 34. OCH₂C₆H₄OCH₂CONH₂(2, 3, or 4) CH₃ 35. OCH₂C₆H₃(CN)₂(3,5) H 36. OCH₂C₆H₃(CN)₂(3,5) CH₃ 37. OCH₂C₆H₃(CONH₂)₂(3,5) H 38. OCH₂C₆H₃(CONH₂)₂(3,5) CH₃ 39. OCH₂C₆H₄—NO₂(2, 3, or 4) H 40. OCH₂C₆H₄—NO₂(2, 3, or 4) CH₃ 41. OCH₂C₆H₄—CF₃(2, 3, or 4) H 42. OCH₂C₆H₄—CF₃(2, 3, or 4) CH₃ 43. OCH₂C₆H₄—CH₃(2, 3, or 4) H 44. OCH₂C₆H₄—CH₃(2, 3, or 4) CH₃ 45. OCH₂C₆H₄—NHSO₂CH₃(2, 3, or 4) H 46. OCH₂C₆H₄—NHSO₂CH₃(2, 3, or 4) CH₃ 47. OCH₂C₆H₄C₆H₄CN(2, 3, or 4) H 48. OCH₂C₆H₄C₆H₄CN(2, 3, or 4) CH₃ 49. OCH₂C₆H₄C₆H₄CONH₂(2, 3, or 4) H 50. OCH₂C₆H₄C₆H₄CONH₂(2, 3, or 4) CH₃ 51. OCH₂C₆H₄C₆H₄CO₂H(2, 3, or 4) H 52. OCH₂C₆H₄C₆H₄CO₂H(2, 3, or 4) CH₃

TABLE VIIIb

Ex. # X′ R¹ 1. NO₂ H 2. NO₂ CH₃ 3. CN H 4. CN CH₃ 5. CONH₂ H 6. CONH₂ CH₃ 7. CO₂H H 8. CO₂H CH₃ 9. NHSO₂CH₃ H 10. NHSO₂CH₃ CH₃ 11. OCH₂C₆H₅ H 12. OCH₂C₆H₅ CH₃ 13. OCH₂CH₂C₆H₅ H 14. OCH₂C₆H₄C₆H₅ H 15. OCH₂C₆H₄C₆H₅ CH₃ 16. OCH₂CH₂C₆H₅ CH₃ 17. OCH₂C₆H₄—Cl(2, 3, or 4) H 18. OCH₂C₆H₄—Cl(2, 3, or 4) CH₃ 19. OCH₂C₆H₄—OCH₃(2, 3, or 4) H 20. OCH₂C₆H₄—OCH₃(2, 3, or 4) CH₃ 21. OCH₂C₆H₄—F(2, 3, or 4) H 22. OCH₂C₆H₄—F(2, 3, or 4) CH₃ 23. OCH₂C₆H₄CN(2, 3, or 4) H 24. OCH₂C₆H₄CN(2, 3, or 4) CH₃ 25. OCH₂C₆H₄CONH₂(2, 3, or 4) H 26. OCH₂C₆H₄CONH₂(2, 3, or 4) CH₃ 27. OCH₂C₆H₄CH₂CN(2, 3, or 4) H 28. OCH₂C₆H₄CH₂CN(2, 3, or 4) CH₃ 29. OCH₂C₆H₄CH₂CONH₂(2, 3, or 4) H 30. OCH₂C₆H₄CH₂CONH₂(2, 3, or 4) CH₃ 31. OCH₂C₆H₄OCH₂CN(2, 3, or 4) H 32. OCH₂C₆H₄OCH₂CN(2, 3, or 4)CH₃ 33. OCH₂C₆H₄OCH₂CONH₂(2, 3, or 4) H 34. OCH₂C₆H₄OCH₂CONH₂(2, 3, or 4) CH₃ 35. OCH₂C₆H₃(CN)₂(3, 5) H 36. OCH₂C₆H₃(CN)₂(3, 5) CH₃ 37. OCH₂C₆H₃(CONH₂)₂(3, 5) H 38. OCH₂C₆H₃(CONH₂)₂(3, 5) CH₃ 39. OCH₂C₆H₄—NO₂(2, 3, or 4) H 40. OCH₂C₆H₄—NO₂(2, 3, or 4) CH₃ 41. OCH₂C₆H₄—CF₃(2, 3, or 4) H 42. OCH₂C₆H₄—CF₃(2, 3, or 4) CH₃ 43. OCH₂C₆H₄—CH₃(2, 3, or 4) H 44. OCH₂C₆H₄—CH₃(2, 3, or 4) CH₃ 45. OCH₂C₆H₄—NHSO₂CH₃(2, 3, or 4) H 46. OCH₂C₆H₄—NHSO₂CH₃(2, 3, or 4) CH₃ 47. OCH₂C₆H₄C₆H₄CN(2, 3, or 4) H 48. OCH₂C₆H₄C₆H₄CN(2, 3, or 4) CH₃ 49. OCH₂C₆H₄C₆H₄CONH₂(2, 3, or 4) H 50. OCH₂C₆H₄C₆H₄CONH₂(2, 3, or 4) CH₃ 51. OCH₂C₆H₄C₆H₄CO₂H(2, 3, or 4) H 52. OCH₂C₆H₄C₆H₄CO₂H(2, 3, or 4) CH₃

TABLE VIIIc

Ex. # X R¹ 1. NHCH₂C₆H₅ H 2. NHCH₂C₆H₅ CH₃ 3. NHCH₂C₆H₄C₆H₅ H 4. NHCH₂C₆H₄C₆H₅ CH₃ 5. NHCH₂CH₂C₆H₅ H 6. NHCH₂CH₂C₆H₅ CH₃ 7. NHCH₂C₆H₄—Cl(2, 3, or 4) H 8. NHCH₂C₆H₄—Cl(2, 3, or 4) CH₃ 9. NHCH₂C₆H₄—OCH₃(2, 3, or 4) H 10. NHCH₂C₆H₄—OCH₃(2, 3, or 4) CH₃ 11. NHCH₂C₆H₄—F(2, 3, or 4) H 12. NHCH₂C₆H₄—F(2, 3, or 4) CH₃ 13. NHCH₂C₆H₄CN(2, 3, or 4) H 14. NHCH₂C₆H₄CN(2, 3, or 4) CH₃ 15. NHCH₂C₆H₄CONH₂(2, 3, or 4) H 16. NHCH₂C₆H₄CONH₂(2, 3, or 4) CH₃ 17. NHCH₂C₆H₄CH₂CN(2, 3, or 4) H 18. NHCH₂C₆H₄CH₂CN(2, 3, or 4) CH₃ 19. NHCH₂C₆H₄CH₂CONH₂(2, 3, or 4) H 20. NHCH₂C₆H₄CH₂CONH₂(2, 3, or 4) CH₃ 21. NHCH₂C₆H₄OCH₂CN(2, 3, or 4) H 22. NHCH₂C₆H₄OCH₂CN(2, 3, or 4) CH₃ 23. NHCH₂C₆H₄OCH₂CONH₂(2, 3, or 4) H 24. NHCH₂C₆H₄OCH₂CONH₂(2, 3, or 4) CH₃ 25. NHCH₂C₆H₃(CN)₂(3, 5) H 26. NHCH₂C₆H₃(CN)₂(3, 5) CH₃ 27. NHCH₂C₆H₃(CONH₂)₂(3, 5) H 28. NHCH₂C₆H₃(CONH₂)₂(3, 5) CH₃ 29. NHCH₂C₆H₄—NO₂(2, 3, or 4) H 30. NHCH₂C₆H₄—NO₂(2, 3, or 4) CH₃ 31. NHCH₂C₆H₄—CF₃(2, 3, or 4) H 32. NHCH₂C₆H₄—CF₃(2, 3, or 4) CH₃ 33. NHCH₂C₆H₄—CH₃(2, 3, or 4) H 34. NHCH₂C₆H₄—CH₃(2, 3, or 4) CH₃ 35. NHCH₂C₆H₄—NHSO₂CH₃(2, 3, or 4) H 36. NHCH₂C₆H₄—NHSO₂CH₃(2, 3, or 4) CH₃ 37. NHCH₂C₆H₄C₆H₄CN(2, 3, or 4) H 38. NHCH₂C₆H₄C₆H₄CN(2, 3, or 4) CH₃ 39. NHCH₂C₆H₄C₆H₄CONH₂(2, 3, or 4) H 40. NHCH₂C₆H₄C₆H₄CONH₂(2, 3, or 4) CH₃ 41. NHCH₂C₆H₄C₆H₄CO₂H(2, 3, or 4) H 42. NHCH₂C₆H₄C₆H₄CO₂H(2, 3, or 4) CH₃

TABLE VIIId

1. NHCH₂C₆H₅ H 2. NHCH₂C₆H₅ CH₃ 3. NHCH₂C₆H₄C₆H₅ H 4. NHCH₂C₆H₄C₆H₅ CH₃ 5. NHCH₂CH₂C₆H₅ H 6. NHCH₂CH₂C₆H₅ CH₃ 7. NHCH₂C₆H₄—Cl(2, 3, or 4) H 8. NHCH₂C₆H₄—Cl(2, 3, or 4) CH₃ 9. NHCH₂C₆H₄—OCH₃(2, 3, or 4) H 10. NHCH₂C₆H₄—OCH₃(2, 3, or 4) CH₃ 11. NHCH₂C₆H₄—F(2, 3, or 4) H 12. NHCH₂C₆H₄—F(2, 3, or 4) CH₃ 13. NHCH₂C₆H₄CN(2, 3, or 4) H 14. NHCH₂C₆H₄CN(2, 3, or 4) CH₃ 15. NHCH₂C₆H₄CONH₂(2, 3, or 4) H 16. NHCH₂C₆H₄CONH₂(2, 3, or 4) CH₃ 17. NHCH₂C₆H₄CH₂CN(2, 3, or 4) H 18. NHCH₂C₆H₄CH₂CN(2, 3, or 4) CH₃ 19. NHCH₂C₆H₄CH₂CONH₂(2, 3, or 4) H 20. NHCH₂C₆H₄CH₂CONH₂(2, 3, or 4) CH₃ 21. NHCH₂C₆H₄OCH₂CN(2, 3, or 4) H 22. NHCH₂C₆H₄OCH₂CN(2, 3, or 4) CH₃ 23. NHCH₂C₆H₄OCH₂CONH₂(2, 3, or 4) H 24. NHCH₂C₆H₄OCH₂CONH₂(2, 3, or 4) CH₃ 25. NHCH₂C₆H₃(CN)₂(3, 5) H 26. NHCH₂C₆H₃(CN)₂(3, 5) CH₃ 27. NHCH₂C₆H₃(CONH₂)₂(3, 5) H 28. NHCH₂C₆H₃(CONH₂)₂(3, 5) CH₃ 29. NHCH₂C₆H₄—NO₂(2, 3, or 4) H 30. NHCH₂C₆H₄—NO₂(2, 3, or 4) CH₃ 31. NHCH₂C₆H₄—CF₃(2, 3, or 4) H 32. NHCH₂C₆H₄—CF₃(2, 3, or 4) CH₃ 33. NHCH₂C₆H₄—CH₃(2, 3, or 4) H 34. NHCH₂C₆H₄—CH₃(2, 3, or 4) CH₃ 35. NHCH₂C₆H₄—NHSO₂CH₃(2, 3, or 4) H 36. NHCH₂C₆H₄—NHSO₂CH₃(2, 3, or 4) CH₃ 37. NHCH₂C₆H₄C₆H₄CN(2, 3, or 4) H 38. NHCH₂C₆H₄C₆H₄CN(2, 3, or 4) CH₃ 39. NHCH₂C₆H₄C₆H₄CONH₂(2, 3, or 4) H 40. NHCH₂C₆H₄C₆H₄CONH₂(2, 3, or 4) CH₃ 41. NHCH₂C₆H₄C₆H₄CO₂H(2, 3, or 4) H 42. NHCH₂C₆H₄C₆H₄CO₂H(2, 3, or 4) CH₃

TABLE IXa

Ex # X R¹ 1. O(CH₂CH₂O)₂CH₂CH₂OH H 2. O(CH₂CH₂O)₂CH₂CH₂OH CH₃ 3. O(CH₂CH₂O)₂CH₂CH₂OCH₃ H 4. O(CH₂CH₂O)₂CH₂CH₂OCH₃ CH₃ 5. O(CH₂CH₂O)₃CH₂CH₂OH H 6. O(CH₂CH₂O)₃CH₂CH₂OH CH₃ 7. O(CH₂CH₂O)₃CH₂CH₂OCH₃ H 8. O(CH₂CH₂O)₃CH₂CH₂OCH₃ CH₃ 9. O(CH₂CH₂O)₄CH₂CH₂OH H 10. O(CH₂CH₂O)₄CH₂CH₂OH CH₃ 11. O(CH₂CH₂O)₄CH₂CH₂OCH₃ H 12. O(CH₂CH₂O)₄CH₂CH₂OCH₃ CH₃ 13. O(CH₂CH₂O)₅CH₂CH₂OH H 14. O(CH₂CH₂O)₅CH₂CH₂OH CH₃ 15. O(CH₂CH₂O)₅CH₂CH₂OCH₃ H 16. O(CH₂CH₂O)₅CH₂CH₂OCH₃ CH₃ 17. O(CH₂CH₂O)₇CH₂CH₂OH H 18. O(CH₂CH₂O)₇CH₂CH₂OH CH₃ 19. O(CH₂CH₂O)₇CH₂CH₂OCH₃ H 20. O(CH₂CH₂O)₇CH₂CH₂OCH₃ CH₃ 21. O(CH₂CH₂O)₉CH₂CH₂OH H 22. O(CH₂CH₂O)₉CH₂CH₂OH CH₃ 23. O(CH₂CH₂O)₉CH₂CH₂OCH₃ H 24. O(CH₂CH₂O)₉CH₂CH₂OCH₃ CH₃

TABLE IXb

Ex # X R¹ 1. O(CH₂CH₂O)₂CH₂CH₂OH H 2. O(CH₂CH₂O)₂CH₂CH₂OH CH₃ 3. O(CH₂CH₂O)₂CH₂CH₂OCH₃ H 4. O(CH₂CH₂O)₂CH₂CH₂OCH₃ CH₃ 5. O(CH₂CH₂O)₃CH₂CH₂OH H 6. O(CH₂CH₂O)₃CH₂CH₂OH CH₃ 7. O(CH₂CH₂O)₃CH₂CH₂OCH₃ H 8. O(CH₂CH₂O)₃CH₂CH₂OCH₃ CH₃ 9. O(CH₂CH₂O)₄CH₂CH₂OH H 10. O(CH₂CH₂O)₄CH₂CH₂OH CH₃ 11. O(CH₂CH₂O)₄CH₂CH₂OCH₃ H 12. O(CH₂CH₂O)₄CH₂CH₂OCH₃ CH₃ 13. O(CH₂CH₂O)₅CH₂CH₂OH H 14. O(CH₂CH₂O)₅CH₂CH₂OH CH₃ 15. O(CH₂CH₂O)₅CH₂CH₂OCH₃ H 16. O(CH₂CH₂O)₅CH₂CH₂OCH₃ CH₃ 17. O(CH₂CH₂O)₇CH₂CH₂OH H 18. O(CH₂CH₂O)₇CH₂CH₂OH CH₃ 19. O(CH₂CH₂O)₇CH₂CH₂OCH₃ H 20. O(CH₂CH₂O)₇CH₂CH₂OCH₃ CH₃ 21. O(CH₂CH₂O)₉CH₂CH₂OH H 22. O(CH₂CH₂O)₉CH₂CH₂OH CH₃ 23. O(CH₂CH₂O)₉CH₂CH₂OCH₃ H 24. O(CH₂CH₂O)₉CH₂CH₂OCH₃ CH₃

TABLE Xa

Number X Q R¹ 1. O(CH₂CH₂O)₂CH₂CH₂OH CH₃ H 2. O(CH₂CH₂O)₂CH₂CH₂OH CH₃ CH₃ 3. O(CH₂CH₂O)₂CH₂CH₂OCH₃ CH₃ H 4. O(CH₂CH₂O)₂CH₂CH₂OCH₃ CH₃ CH₃ 5. O(CH₂CH₂O)₃CH₂CH₂OH CH₃ H 6. O(CH₂CH₂O)₃CH₂CH₂OH CH₃ CH₃ 7. O(CH₂CH₂O)₃CH₂CH₂OCH₃ CH₃ H 8. O(CH₂CH₂O)₃CH₂CH₂OCH₃ CH₃ CH₃ 9. O(CH₂CH₂O)₄CH₂CH₂OH CH₃ H 10. O(CH₂CH₂O)₄CH₂CH₂OH CH₃ CH₃ 11. O(CH₂CH₂O)₄CH₂CH₂OCH₃ CH₃ H 12. O(CH₂CH₂O)₄CH₂CH₂OCH₃ CH₃ CH₃ 13. O(CH₂CH₂O)₅CH₂CH₂OH CH₃ H 14. O(CH₂CH₂O)₅CH₂CH₂OH CH₃ CH₃ 15. O(CH₂CH₂O)₅CH₂CH₂OCH₃ CH₃ H 16. O(CH₂CH₂O)₅CH₂CH₂OCH₃ CH₃ CH₃ 17. O(CH₂CH₂O)₇CH₂CH₂OH CH₃ H 18. O(CH₂CH₂O)₇CH₂CH₂OH CH₃ CH₃ 19. O(CH₂CH₂O)₇CH₂CH₂OCH₃ CH₃ H 20. O(CH₂CH₂O)₇CH₂CH₂OCH₃ CH₃ CH₃ 21. O(CH₂CH₂O)₉CH₂CH₂OH CH₃ H 22. O(CH₂CH₂O)₉CH₂CH₂OH CH₃ CH₃ 23. O(CH₂CH₂O)₉CH₂CH₂OCH₃ CH₃ H 24. O(CH₂CH₂O)₉CH₂CH₂OCH₃ CH₃ CH₃ 25. O(CH₂CH₂O)₂CH₂CH₂OH CH₂C≡CH H 26. O(CH₂CH₂O)₂CH₂CH₂OH CH₂C≡CH CH₃ 27. O(CH₂CH₂O)₂CH₂CH₂OCH₃ CH₂C≡CH H 28. O(CH₂CH₂O)₂CH₂CH₂OCH₃ CH₂C≡CH CH₃ 29. O(CH₂CH₂O)₃CH₂CH₂OH CH₂C≡CH H 30. O(CH₂CH₂O)₃CH₂CH₂OH CH₂C≡CH CH₃ 31. O(CH₂CH₂O)₃CH₂CH₂OCH₃ CH₂C≡CH H 32. O(CH₂CH₂O)₃CH₂CH₂OCH₃ CH₂C≡CH CH₃ 33. O(CH₂CH₂O)₄CH₂CH₂OH CH₂C≡CH H 34. O(CH₂CH₂O)₄CH₂CH₂OH CH₂C≡CH CH₃ 35. O(CH₂CH₂O)₄CH₂CH₂OCH₃ CH₂C≡CH H 36. O(CH₂CH₂O)₄CH₂CH₂OCH₃ CH₂C≡CH CH₃ 37. O(CH₂CH₂O)₅CH₂CH₂OH CH₂C≡CH H 38. O(CH₂CH₂O)₅CH₂CH₂OH CH₂C≡CH CH₃ 39. O(CH₂CH₂O)₅CH₂CH₂OCH₃ CH₂C≡CH H 40. O(CH₂CH₂O)₅CH₂CH₂OCH₃ CH₂C≡CH CH₃ 41. O(CH₂CH₂O)₇CH₂CH₂OH CH₂C≡CH H 42. O(CH₂CH₂O)₇CH₂CH₂OH CH₂C≡CH CH₃ 43. O(CH₂CH₂O)₇CH₂CH₂OCH₃ CH₂C≡CH H 44. O(CH₂CH₂O)₇CH₂CH₂OCH₃ CH₂C≡CH CH₃ 45. O(CH₂CH₂O)₉CH₂CH₂OH CH₂C≡CH H 46. O(CH₂CH₂O)₉CH₂CH₂OH CH₂C≡CH CH₃ 47. O(CH₂CH₂O)₉CH₂CH₂OCH₃ CH₂C≡CH H 48. O(CH₂CH₂O)₉CH₂CH₂OCH₃ CH₂C≡CH CH₃

TABLE Xb

Number X Q R¹ 1. O(CH₂CH₂O)₂CH₂CH₂OH CH₃ H 2. O(CH₂CH₂O)₂CH₂CH₂OH CH₃ CH₃ 3. O(CH₂CH₂O)₂CH₂CH₂OCH₃ CH₃ H 4. O(CH₂CH₂O)₂CH₂CH₂OCH₃ CH₃ CH₃ 5. O(CH₂CH₂O)₃CH₂CH₂OH CH₃ H 6. O(CH₂CH₂O)₃CH₂CH₂OH CH₃ CH₃ 7. O(CH₂CH₂O)₃CH₂CH₂OCH₃ CH₃ H 8. O(CH₂CH₂O)₃CH₂CH₂OCH₃ CH₃ CH₃ 9. O(CH₂CH₂O)₄CH₂CH₂OH CH₃ H 10. O(CH₂CH₂O)₄CH₂CH₂OH CH₃ CH₃ 11. O(CH₂CH₂O)₄CH₂CH₂OCH₃ CH₃ H 12. O(CH₂CH₂O)₄CH₂CH₂OCH₃ CH₃ CH₃ 13. O(CH₂CH₂O)₅CH₂CH₂OH CH₃ H 14. O(CH₂CH₂O)₅CH₂CH₂OH CH₃ CH₃ 15. O(CH₂CH₂O)₅CH₂CH₂OCH₃ CH₃ H 16. O(CH₂CH₂O)₅CH₂CH₂OCH₃ CH₃ CH₃ 17. O(CH₂CH₂O)₇CH₂CH₂OH CH₃ H 18. O(CH₂CH₂O)₇CH₂CH₂OH CH₃ CH₃ 19. O(CH₂CH₂O)₇CH₂CH₂OCH₃ CH₃ H 20. O(CH₂CH₂O)₇CH₂CH₂OCH₃ CH₃ CH₃ 21. O(CH₂CH₂O)₉CH₂CH₂OH CH₃ H 22. O(CH₂CH₂O)₉CH₂CH₂OH CH₃ CH₃ 23. O(CH₂CH₂O)₉CH₂CH₂OCH₃ CH₃ H 24. O(CH₂CH₂O)₉CH₂CH₂OCH₃ CH₃ CH₃ 25. O(CH₂CH₂O)₂CH₂CH₂OH CH₂C≡CH H 26. O(CH₂CH₂O)₂CH₂CH₂OH CH₂C≡CH CH₃ 27. O(CH₂CH₂O)₂CH₂CH₂OCH₃ CH₂C≡CH H 28. O(CH₂CH₂O)₂CH₂CH₂OCH₃ CH₂C≡CH CH₃ 29. O(CH₂CH₂O)₃CH₂CH₂OH CH₂C≡CH H 30. O(CH₂CH₂O)₃CH₂CH₂OH CH₂C≡CH CH₃ 31. O(CH₂CH₂O)₃CH₂CH₂OCH₃ CH₂C≡CH H 32. O(CH₂CH₂O)₃CH₂CH₂OCH₃ CH₂C≡CH CH₃ 33. O(CH₂CH₂O)₄CH₂CH₂OH CH₂C≡CH H 34. O(CH₂CH₂O)₄CH₂CH₂OH CH₂C≡CH CH₃ 35. O(CH₂CH₂O)₄CH₂CH₂OCH₃ CH₂C≡CH H 36. O(CH₂CH₂O)₄CH₂CH₂OCH₃ CH₂C≡CH CH₃ 37. O(CH₂CH₂O)₅CH₂CH₂OH CH₂C≡CH H 38. O(CH₂CH₂O)₅CH₂CH₂OH CH₂C≡CH CH₃ 39. O(CH₂CH₂O)₅CH₂CH₂OCH₃ CH₂C≡CH H 40. O(CH₂CH₂O)₅CH₂CH₂OCH₃ CH₂C≡CH CH₃ 41. O(CH₂CH₂O)₇CH₂CH₂OH CH₂C≡CH H 42. O(CH₂CH₂O)₇CH₂CH₂OH CH₂C≡CH CH₃ 43. O(CH₂CH₂O)₇CH₂CH₂OCH₃ CH₂C≡CH H 44. O(CH₂CH₂O)₇CH₂CH₂OCH₃ CH₂C≡CH CH₃ 45. O(CH₂CH₂O)₉CH₂CH₂OH CH₂C≡CH H 46. O(CH₂CH₂O)₉CH₂CH₂OH CH₂C≡CH CH₃ 47. O(CH₂CH₂O)₉CH₂CH₂OCH₃ CH₂C≡CH H 48. O(CH₂CH₂O)₉CH₂CH₂OCH₃ CH₂C≡CH CH₃

Numerous modifications and variations of the present invention are possible in light of the above teachings. It is therefore to be understood that within the scope of the appended claims, the invention may be practiced otherwise that as specifically described herein. 

1. A compound of formula I or II, or a stereoisomer or a pharmaceutically acceptable salt thereof:

wherein: R, at each occurrence, is independently selected from H, C₁₋₆ alkyl, C₂₋₆ alkenyl, and C₂₋₆ alkynyl; R¹ is selected from H, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, (CH₂)_(m)CO₂R, C₂₋₆ alkenyl-CO₂R, CH₂CH(NHAc)CO₂R, CH₂CH(NHR)CO₂R, and, (CH₂)_(n)PO(OR)₂; R² is selected from H, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, (CH₂)_(m)CO₂R, C₂₋₆ alkenyl-CO₂R, (CH₂)_(n)CON(R)₂, (CH₂)_(n)PO(OR)₂, and (CH₂)_(n)-tetrazole; X and X¹ are independently selected from H, OR, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, CF₃, nitro, N(R)₂, (CH₂)_(m)-tetrazole, (CH₂)_(m)CO₂R, (CH₂)_(m)CONR₂, (CH₂)_(m)CN, O(CH₂)_(n)CN, O(CH₂)_(n)-tetrazole, O(CH₂)_(n)CO₂R, O(CH₂)_(n)CON(R)₂, O—C₂₋₆ alkenyl-CO₂R, O(CH₂)_(n)PO(OR)₂, NR—C₂₋₄ alkenyl, NRSO₂CH₃, NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)CON(R)₂, NR—C₂₋₄ alkenyl-CO₂R, NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)SO₂OR, NR(CH₂)_(n)-tetrazole, NRCO(CH₂)_(n)CO₂R, NRCO(CH₂)_(n)CON(R)₂, SO₂NRCH₃, OCH₂CHMCONRCH₂CO₂R, CH₂-aryl, O(CH₂)_(n)PO(OR)₂, O(CH₂)₅SO₂OR, (CH₂)_(n)N⁺(R)₃A⁻, OCH₂(CH₂)_(n)N⁺(R)₃A⁻, O(CH₂)_(n)-biphenyl, O(CH₂)_(n)-biphenyl-(CH₂)_(m)CO₂R, O(CH₂)_(n)-biphenyl-(CH₂)_(m)tetrazole, O(CH₂)_(n)-biphenyl-(CH₂)_(m)CN, O(CH₂)_(n)-biphenyl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-biphenyl, NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CO₂R, NR(CH₂)_(n)-biphenyl-(CH₂)_(m)tetrazole, NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CN, NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl, O(CH₂)_(n)-heteroaryl, NR(CH₂)_(n)-aryl, NR(CH₂)_(n)-heteroaryl, O(CH₂)_(n)-aryl(CH₂)_(m)CO₂R, O(CH₂)_(n)-aryl-C₂₋₆ alkenyl-CO₂R, O(CH₂)_(n)-aryl(CH₂)_(m)-tetrazole, O(CH₂)_(n)-aryl(CH₂)_(m)CN, O(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl(CH₂)_(m)—PO(OR)₂, O(CH₂)_(n)-aryl-O(CH₂)_(n)CO₂R, O(CH₂)_(n)-aryl-O—C₂₋₆ alkenyl-CO₂R, O(CH₂)_(n)-arylO(CH₂)_(n)-tetrazole, O(CH₂)_(n)-arylO(CH₂)_(n)CN, O(CH₂)_(n)-arylO(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-arylO(CH₂)_(n)—PO(OR)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CO₂R, O(CH₂)_(n)-aryl-NRC₂₋₆ alkenyl-CO₂R, O(CH₂)_(n)-aryl-NR(CH₂)_(n)-tetrazole, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CN, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)—PO(OR)₂, NR(CH₂)_(n)-aryl(CH₂)_(m)CO₂R, NR(CH₂)_(n)-aryl-C₂₋₆ alkenyl-CO₂R, NR(CH₂)_(n)-aryl(CH₂)_(m)-tetrazole, NR(CH₂)_(n)-aryl(CH₂)_(m)CN, NR(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-aryl(CH₂)_(m)—PO(OR)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)-aryl-NR—C₂₋₆ alkenyl-CO₂R, NR(CH₂)_(n)-aryl-NR(CH₂)_(n-)tetrazole, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CN, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)-arylO(CH₂)_(n)CO₂R, NR(CH₂)_(n)-aryl-O—C₂₋₆ alkenyl-CO₂R, NR(CH₂)_(n)-aryl-O(CH₂)_(n-)tetrazole, NR(CH₂)_(n)-arylO(CH₂)_(n)CN, NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-arylO(CH₂)_(n)PO(OR)₂, O(CH₂)_(n)-heteroaryl(CH₂)_(m)CO₂R, O(CH₂)_(n)-heteroaryl-C₂₋₆ alkenyl-CO₂R, O(CH₂)_(n)-heteroaryl(CH₂)_(m)-tetrazole, O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CN, O(CH₂)_(n)-heteroaryl(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-heteroaryl(CH₂)_(m)—PO(OR)₂, O(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CO₂R, O(CH₂)_(n)-heteroaryl-O—C₂₋₆ alkenyl-CO₂R, O(CH₂)_(n)-heteroarylO(CH₂)_(n)-tetrazole, O(CH₂)_(n)-heteroaryl O(CH₂)_(n)CN, O(CH₂)_(n)-heteroarylO(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroarylO(CH₂), —PO(OR)₂, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CO₂R, O(CH₂)_(n)-heteroaryl-NR—C₂₋₆ alkenyl-CO₂R, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)-tetrazole, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CN, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)—PO(OR)₂, NR(CH₂)_(n)-heteroaryl(CH₂)_(m)CO₂R, NR(CH₂)_(n)-heteroaryl-C₂₋₆ alkenyl-CO₂R, NR(CH₂)_(n)-heteroaryl(CH₂)_(m)-tetrazole, NR(CH₂)_(n)-heteroaryl(CH₂)_(m)CN, NR(CH₂)_(n)-heteroaryl(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-heteroaryl(CH₂)_(m)—PO(OR)₂, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)-heteroaryl-NR—C₂₋₆ alkenyl-CO₂R, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n-)tetrazole, NR(CH₂)_(n) heteroaryl-NR(CH₂)_(n)CN, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CO₂R, NR(CH₂)_(n)-heteroaryl-O—C₂₋₆ alkenyl-CO₂R, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n-)tetrazole, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CN, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroarylO(CH₂)_(n)PO(OR)₂, and O(CH₂CH₂O)_(p)CH₂CH₂OR³, where heteroaryl is a 5-12 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X² and tetrazole is substituted with 0-1 R; R³ is selected from H, C₁₋₆ alkyl, and aryl-C₁₋₆ alkyl-; X², at each occurrence, is independently selected from H, OR, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, —CN, C(O)NR₂, NRSO₂CH₃, and SO₂N(R)C₁₋₄alkyl; A⁻, at each occurrence, is a counterion; Y is selected from O and H₂; Z is selected from H, OR, O(CH₂)_(n)CO₂R, O(CH₂)_(n)CONH₂, OCH₂CHMCONRCH₂CO₂R, OCH₂CH(NHC(O)CH₃)CO₂R, OCH₂CH(NHR)CO₂R, O(CH₂)_(n)PO(OR)₂, O(CH₂)_(n)SO₂OR, O(CH₂)_(n)-tetrazole, O—C₂₋₆ alkenyl, O(CH₂)_(n)-aryl, OCH₂CH₂CONRCH(OR)CO₂R, OCH₂CH₂CONRC(R)₂CH₂SO₂OR, NRR, NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)CONH₂, NRCH₂CHMCONRCH₂CO₂R, NRSO₂R, NRCH₂CH(NHC(O)CH₃)CO₂R, NRCH₂CH(NHR)CO₂R, NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)SO₂OR, NR(CH₂)_(n)-tetrazole, NR—C₂₋₆ alkenyl, NR(CH₂)_(n)-aryl, NRCH₂CH₂CONRCH(OR)CO₂R, NRCH₂CH₂CONRC(R)₂CH₂SO₂OR, and NRCO(CH₂)_(n)CO₂R, O(CH₂)_(n)-aryl-CO₂R, O(CH₂)_(n)-aryl-tetrazole, O(CH₂)_(n)-aryl-CON(R)₂, O(CH₂)_(n)-aryl-PO(OR)₂, NR(CH₂)_(n)-aryl-CO₂R, NR(CH₂)_(n)-aryl-tetrazole, NR(CH₂)_(n)-aryl-CON(R)₂, and NR(CH₂)_(n)-aryl-PO(OR)₂, wherein aryl is substituted with 1-2 X² and tetrazole is substituted with 0-1 R; when Y is H₂, Z¹ is selected from H, OR, O(CH₂)_(n)CO₂R, O(CH₂)_(n)CONH₂, OCH₂CHMCONRCH₂CO₂R, OCH₂CH(NHC(O)CH₃)CO₂R, OCH₂CH(NHR)CO₂R, O(CH₂)_(n)PO(OR)₂, O(CH₂)_(n)SO₂OR, O—C₂₋₆ alkenyl, O(CH₂)_(n)-aryl, NR(CH₂)_(n)-aryl, OCH₂CH₂CONRCH(OR)CO₂R, OCH₂CH₂CONRC(R)₂CH₂SO₂OR, and NRCO(CH₂)_(n)CO₂R, wherein aryl is substituted with 1-2 X²; when Y is O, Z¹ is selected from OR, NRR, NR(CH₂)_(n)CONH₂, NR—C₂₋₆ alkyl O(CH₂)_(n)-aryl, and NR(CH₂)_(n)-aryl, wherein aryl is substituted with 1-2 X²; M is selected from H, C₁₋₆ alkyl, C₃₋₈ cycloalkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, aryl, 5-12 membered heteroaryl consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, (CH₂)_(n)-aryl, and (CH₂)_(n)-5-12 membered heteroaryl consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, wherein aryl and heteroaryl are substituted with 1-2 X²; Q is selected from O⁻, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, (CH₂)_(n)-aryl, and (CH₂)_(n)-5-12 membered heteroaryl consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, wherein aryl and heteroaryl are substituted with 1-2 X²; provided that when Q is other than O⁻, then A⁻ is present; m is selected from 0, 1, 2, 3, and 4; n is selected from 1, 2, 3, and 4; p is selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11; and, provided that in formula I: (a) R is other than H and CH₃, (b) C(═Y)Z is other than CH₃; and/or (c) at least one of R¹, R², X, and X¹ is other than H; further provided that at least one of X and X¹ is other than H, alkyl, alkoxy, hydroxy, and halo.
 2. A compound of claim 1, wherein the compound is of formula Ia, or a stereoisomer or a pharmaceutically acceptable salt thereof:

wherein: R, at each occurrence, is independently selected from H and C₁₋₄ alkyl; R¹ is selected from H and C₁₋₄ alkyl; X and X¹ are independently selected from H, OR, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl, N(R)₂, (CH₂)_(m)CONR₂, (CH₂)_(m)CN, NRSO₂CH₃, NRCO(CH₂)_(n)CON(R)₂, SO₂NRCH₃, CH₂N(C₁₋₄ alkyl)₂, CH₂-aryl, CH₂-heteroaryl, O(CH₂)_(n)-aryl, O(CH₂)_(n)-heteroaryl, NR(CH₂)_(n)-aryl, NR(CH₂)_(n)-heteroaryl, O(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(p)-biphenyl, O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CON(R)₂, NR(CH₂)_(n)-biphenyl, NR(CH₂)_(n)-biphenyl-CN, and NR(CH₂)_(n)-biphenyl-CONH₂, and O(CH₂CH₂O)_(p)CH₂CH₂OR³, where heteroaryl is a 5-10 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S; and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X², R³ is selected from H, C₁₋₄ alkyl, and aryl-C₁₋₄ alkyl-; X², at each occurrence, is independently selected from H, OR, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, —CN, C(O)NR₂, NRSO₂CH₃, and SO₂N(R)C₁₋₄alkyl; and, provided that at least one of X and X¹ is other than H, alkyl, alkoxy, hydroxy, and halo.
 3. A compound of claim 2, wherein: one of X and X¹ is H and the other selected from C₂₋₄ alkenyl, C₂₋₄ alkynyl, CF₃, nitro, O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl, N(R)₂, (CH₂)_(m)CONR₂, (CH₂)_(m)CN, NRCO(CH₂)_(n)CON(R)₂, NRSO₂CH₃, SO₂NRCH₃, CH₂N(C₁₋₄ alkyl)₂, CH₂-aryl, CH₂-heteroaryl, O(CH₂)_(n)-aryl, O(CH₂)_(n)-heteroaryl, NR(CH₂)_(n)-aryl, NR(CH₂)_(n)-heteroaryl, O(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-biphenyl, O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CON(R)₂, NR(CH₂)_(n)-biphenyl, NR(CH₂)_(n)-biphenyl-CN, and NR(CH₂)_(n)-biphenyl-CONH₂, and O(CH₂CH₂O)_(p)CH₂CH₂OR³, where heteroaryl is a 5-10 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S; and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X².
 4. A compound of claim 1, wherein the compound is of formula Ib, or a stereoisomer or a pharmaceutically acceptable salt thereof:

wherein: R, at each occurrence, is independently selected from H and C₁₋₄ alkyl; R¹ is selected from (CH₂)_(m)CO₂R, C₂₋₄ alkenyl-CO₂R, CH₂CH(NHAc)CO₂R, CH₂CH(NHR)CO₂R, and, (CH₂)_(n)PO(OR)₂; X and X¹ are independently selected from H, OR, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl, N(R)₂, (CH₂)_(m)CONR₂, (CH₂)_(m)CN, NRCO(CH₂)_(n)CON(R)₂, NRSO₂CH₃, SO₂NRCH₃, CH₂N(C₁₋₄ alkyl)₂, CH₂-aryl, CH₂-heteroaryl, O(CH₂)_(n)-aryl, O(CH₂)_(n)-heteroaryl, NR(CH₂)_(n)-aryl, NR(CH₂)_(n)-heteroaryl, O(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-biphenyl, O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CONH₂, NR(CH₂)_(n)-biphenyl, NR(CH₂)_(n)-biphenyl-CN, NR(CH₂)_(n)-biphenyl-CONH₂, and O(CH₂CH₂O)_(p)CH₂CH₂OR³, where heteroaryl is a 5-10 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X²; R³ is selected from H, C₁₋₄ alkyl, and aryl-C₁₋₄ alkyl-; X², at each occurrence, is independently selected from H, OR, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, —CN, C(O)NR₂, NRSO₂CH₃, and SO₂N(R)C₁₋₄alkyl; M is selected from H, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, (CH₂)_(n)-aryl, and (CH₂)_(n)-5-10 membered heteroaryl consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, wherein aryl and heteroaryl are substituted with 1-2 X²; and, provided that in formula Ib: (a) R is other than H and CH₃, and/or (b) at least one of R¹, X, and X¹ is other than H; further provided that at least one of X and X¹ is other than H, alkyl, alkoxy, hydroxy, and halo.
 5. A compound of claim 4, wherein: one of X and X¹ is H and the other selected from C₂₋₄ alkenyl, C₂₋₄ alkynyl, CF₃, nitro, O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl, N(R)₂, (CH₂)_(m)CONR₂, (CH₂)_(m)CN, NRCO(CH₂)_(n)CON(R)₂, NRSO₂CH₃, SO₂NRCH₃, CH₂N(C₁₋₄ alkyl)₂, CH₂-aryl, CH₂-heteroaryl, O(CH₂)_(n)-aryl, O(CH₂)_(n)-heteroaryl, NR(CH₂)_(n)-aryl, NR(CH₂)_(n)-heteroaryl, O(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-biphenyl, O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CONH₂, NR(CH₂)_(n)-biphenyl, NR(CH₂)_(n)-biphenyl-CN, NR(CH₂)_(n)-biphenyl-CONH₂, and O(CH₂CH₂O)_(p)CH₂CH₂OR³, where heteroaryl is a 5-10 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X².
 6. A compound of claim 1, wherein the compound is of formula Ic, or a stereoisomer or a pharmaceutically acceptable salt thereof:

wherein: R, at each occurrence, is independently selected from H and C₁₋₄ alkyl; R¹ is selected from H and C₁₋₄ alkyl; X and X¹ are independently selected from H, OR, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl, N(R)₂, (CH₂)_(m)CONR₂, (CH₂)_(m)CN, NRCO(CH₂)_(n)CON(R)₂, NRSO₂CH₃, SO₂NRCH₃, CH₂N(C₁₋₄ alkyl)₂, CH₂-aryl, CH₂-heteroaryl, O(CH₂)_(n)-aryl, O(CH₂)_(n)-heteroaryl, NR(CH₂)_(n)-aryl, NR(CH₂)_(n)-heteroaryl, O(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, NR(CH₂)-aryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(b)-biphenyl, O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CONH₂, NR(CH₂)_(n)-biphenyl, NR(CH₂)_(n)-biphenyl-CN, NR(CH₂)_(n)-biphenyl-CONH₂, and O(CH₂CH₂O)_(p)CH₂CH₂OR³, where heteroaryl is a 5-10 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X²; R³ is selected from H, C₁₋₄ alkyl, and aryl-C₁₋₄ alkyl-; X², at each occurrence, is independently selected from H, OR, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, —CN, C(O)NR₂, NRSO₂CH₃, and SO₂N(R)C₁₋₄alkyl; A⁻ is selected from Cl⁻ and Br⁻; Z is selected from O(CH₂)_(n)CO₂R, O(CH₂)_(n)CONH₂, O(CH₂)_(n)PO(OR)₂, O(CH₂)_(n)SO₂OR, O(CH₂)_(n)-tetrazole, NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)CONH₂, NRCH₂CHMCONRCH₂CO₂R, NRSO₂R, NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)SO₂OR, NR(CH₂)_(n)-tetrazole, NRCO(CH₂)_(n)CO₂R, O(CH₂)_(n)-phenyl-CO₂R, O(CH₂)_(n)-phenyl-tetrazole, O(CH₂)_(n)-phenyl-CON(R)₂, O(CH₂)_(n)-phenyl-PO₃(R)₂, NR(CH₂)_(n)-phenyl-CO₂R, NR(CH₂)_(n)-phenyl-tetrazole, NR(CH₂)_(n)-phenyl-CON(R)₂, and NR(CH₂)_(n)-phenyl-PO₃(R)₂, wherein phenyl is substituted with 1-2 X² and tetrazole is substituted with 0-1 R; and, M is selected from H, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, (CH₂)_(n)-aryl, and (CH₂)_(n)-5-10 membered heteroaryl consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, wherein aryl and heteroaryl are substituted with 1-2 X²; and, provided that at least one of X and X¹ is other than H, alkyl, alkoxy, hydroxy, and halo.
 7. A compound of claim 6, wherein: one of X and X¹ is H and the other selected from C₂₋₄ alkenyl, C₂₋₄ alkynyl, CF₃, nitro, O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl, N(R)₂, (CH₂)_(m)CONR₂, (CH₂)_(m)CN, NRCO(CH₂)_(n)CON(R)₂, NRSO₂CH₃, SO₂NRCH₃, CH₂N(C₁₋₄ alkyl)₂, CH₂-aryl, CH₂-heteroaryl, O(CH₂)_(n)-aryl, O(CH₂)_(n)-heteroaryl, NR(CH₂)_(n)-aryl, NR(CH₂)_(n)-heteroaryl, O(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-biphenyl, O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CONH₂, NR(CH₂)_(n)-biphenyl, NR(CH₂)_(n)-biphenyl-CN, NR(CH₂)_(n)-biphenyl-CONH₂, and O(CH₂CH₂O)_(p)CH₂CH₂OR³, where heteroaryl is a 5-10 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X².
 8. A compound of claim 1, wherein the compound is of formula Ic, or a stereoisomer or a pharmaceutically acceptable salt thereof:

wherein: R, at each occurrence, is independently selected from H and C₁₋₄ alkyl; R¹ is selected from H, C₁₋₄ alkyl, (CH₂)_(m)CO₂R, C₂₋₄ alkenyl-CO₂R, CH₂CH(NHAc)CO₂R, CH₂CH(NHR)CO₂R, and, (CH₂)_(n)PO(OR)₂; X and X¹ are independently selected from H, OR, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, N(R)₂, (CH₂)_(m)-tetrazole, (CH₂)_(m)CO₂R, (CH₂)_(m)CONR₂, (CH₂)_(m)CN, O(CH₂)_(n)CN, O(CH₂)_(n)-tetrazole, O(CH₂)_(n)CO₂R, O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl-CO₂R, O(CH₂)_(n)PO(OR)₂, NR—C₂₋₄ alkenyl, NRSO₂CH₃, NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)CON(R)₂, NR—C₂₋₄ alkenyl-CO₂R, NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)SO₂OR, NR(CH₂)_(n)-tetrazole, NRCO(CH₂)_(n)CO₂R, NRCO(CH₂)_(n)CON(R)₂, SO₂NRCH₃, OCH₂CHMCONRCH₂CO₂R, CH₂-aryl, O(CH₂)_(n)PO(OR)₂, O(CH₂)_(n)SO₂OR, (CH₂)_(n)N⁺(R)₃A⁻, OCH₂(CH₂)_(n)N⁺(R)₃A⁻, O(CH₂)_(n)-biphenyl, O(CH₂)_(n)-biphenyl-(CH₂)_(m)CO₂R, O(CH₂)_(n)-biphenyl-(CH₂)_(m)tetrazole, O(CH₂)_(n)-biphenyl-(CH₂)_(m)CN, O(CH₂)_(n)-biphenyl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-biphenyl, NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CO₂R, NR(CH₂)_(n)-biphenyl-(CH₂)_(m)tetrazole, NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CN, NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl, O(CH₂)_(n)-heteroaryl, NR(CH₂)_(n)-aryl, NR(CH₂)_(n)-heteroaryl, O(CH₂)_(n)-aryl(CH₂)_(m)CO₂R, O(CH₂)_(n)-aryl-C₂₋₄ alkenyl-CO₂R, O(CH₂)_(n)-aryl(CH₂)_(m)-tetrazole, O(CH₂)_(n)-aryl(CH₂)_(m)CN, O(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl(CH₂)_(m)—PO(OR)₂, O(CH₂)_(n)-aryl-O(CH₂)_(n)CO₂R, O(CH₂)_(n)-aryl-O—C₂₋₄ alkenyl-CO₂R, O(CH₂)_(n)-arylO(CH₂)_(n)-tetrazole, O(CH₂)_(n)-arylO(CH₂)_(n)CN, O(CH₂)_(n)-arylO(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-arylO(CH₂)_(n)—PO(OR)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CO₂R, O(CH₂)_(n)-aryl-NRC₂₋₄ alkenyl-CO₂R, O(CH₂)_(n)-aryl-NR(CH₂)_(n)-tetrazole, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CN, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)—PO(OR)₂, NR(CH₂)_(n)-aryl(CH₂)_(m)CO₂R, NR(CH₂)_(n)-aryl-C₂₋₄ alkenyl-CO₂R, NR(CH₂)_(n)-aryl(CH₂)_(m)-tetrazole, NR(CH₂)_(n)-aryl(CH₂)_(m)CN, NR(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-aryl(CH₂)_(m)—PO(OR)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)-aryl-NR—C₂₋₄ alkenyl-CO₂R, NR(CH₂)_(n)-aryl-NR(CH₂)_(n-)tetrazole, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CN, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)-arylO(CH₂)_(n)CO₂R, NR(CH₂)_(n)-aryl-O—C₂₋₄ alkenyl-CO₂R, NR(CH₂)_(n)-aryl-O(CH₂)_(n-)tetrazole, NR(CH₂)_(n)-arylO(CH₂)_(n)CN, NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-arylO(CH₂)_(n)PO(OR)₂, O(CH₂)_(n)-heteroaryl(CH₂)_(m)CO₂R, O(CH₂)_(n)-heteroaryl-C₂₋₄ alkenyl-CO₂R, O(CH₂)_(n)-heteroaryl(CH₂)_(m)-tetrazole, O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CN, O(CH₂)_(n)-heteroaryl(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-heteroaryl(CH₂)_(m)—PO(OR)₂, O(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CO₂R, O(CH₂)_(n)-heteroaryl-O—C₂₋₄ alkenyl-CO₂R, O(CH₂)_(n)-heteroarylO(CH₂)_(n)-tetrazole, O(CH₂)_(n)-heteroaryl O(CH₂)_(n)CN, O(CH₂)_(n)-heteroarylO(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroarylO(CH₂)_(n)—PO(OR)₂, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CO₂R, O(CH₂)_(n)-heteroaryl-NR—C₂₋₄ alkenyl-CO₂R, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)-tetrazole, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CN, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)—PO(OR)₂, NR(CH₂)_(n)-heteroaryl(CH₂)_(m)CO₂R, NR(CH₂)_(n)-heteroaryl-C₂₋₄ alkenyl-CO₂R, NR(CH₂)_(n)-heteroaryl(CH₂)_(m)-tetrazole, NR(CH₂)_(n)-heteroaryl(CH₂)_(m)CN, NR(CH₂)_(n)-heteroaryl(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-heteroaryl(CH₂)_(m)—PO(OR)₂, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)-heteroaryl-NR—C₂₋₄ alkenyl-CO₂R, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n-)tetrazole, NR(CH₂)_(n) heteroaryl-NR(CH₂)_(n)CN, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CO₂R, NR(CH₂)_(n)-heteroaryl-O—C₂₋₄ alkenyl-CO₂R, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n-)tetrazole, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CN, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroarylO(CH₂)_(n)PO(OR)₂, and O(CH₂CH₂O)_(p)CH₂CH₂OR³, where heteroaryl is a 5-12 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X² and tetrazole is substituted with 0-1 R; R³ is selected from H, C₁₋₄ alkyl, and aryl-C₁₋₄ alkyl-; X², at each occurrence, is independently selected from H, OR, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, —CN, C(O)NR₂, NRSO₂CH₃, and SO₂N(R)C₁₋₄alkyl; A⁻, at each occurrence, is selected from Cl⁻ and Br⁻; Z is selected from H, OH, halogen, CF₃, C₁₋₄ alkoxy, O—C₂₋₄ alkenyl, O(CH₂)_(n)CONH₂, OCH₂-aryl, NRR, NR—C₂₋₄ alkenyl, NR(CH₂)_(n)CONH₂, NR(CH₂)_(n)-aryl, and NRCO(CH₂)_(n)CO₂R, wherein aryl is substituted with 1-2 X²; M is selected from H, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, (CH₂)_(n)-aryl, and (CH₂)_(n)-5-10 membered heteroaryl consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S; and, wherein aryl and heteroaryl are substituted with 1-2 X²; and, provided that in formula Ic: (a) R is other than H and CH₃, (b) Z is other than H; and/or (c) at least one of R¹, X, and X¹ is other than H; further provided that at least one of X and X¹ is other than H, alkyl, alkoxy, hydroxy, and halo.
 9. A compound of claim 8, wherein: one of X and X¹ is H and the other selected from C₂₋₄ alkenyl, C₂₋₄ alkynyl, CF₃, nitro, N(R)₂, (CH₂)_(m)-tetrazole, (CH₂)_(m)CO₂R, (CH₂)_(m)CONR₂, (CH₂)_(m)CN, O(CH₂)_(n)CN, O(CH₂)_(n)-tetrazole, O(CH₂)_(n)CO₂R, O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl-CO₂R, O(CH₂)_(n)PO(OR)₂, NR—C₂₋₄ alkenyl, NRSO₂CH₃, NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)CON(R)₂, NR—C₂₋₄ alkenyl-CO₂R, NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)SO₂OR, NR(CH₂)_(n)-tetrazole, NRCO(CH₂)_(n)CO₂R, NRCO(CH₂)_(n)CON(R)₂, SO₂NRCH₃, OCH₂CHMCONRCH₂CO₂R, CH₂-aryl, O(CH₂)_(n)PO(OR)₂, O(CH₂)_(n)SO₂OR, (CH₂)_(n)N⁺(CH₃)₃A⁻, OCH₂(CH₂)_(n)N⁺(CH₃)₃A⁻, O(CH₂)_(n)-biphenyl, O(CH₂)_(n)-biphenyl-(CH₂)_(m)CO₂R, O(CH₂)_(n)-biphenyl-(CH₂)_(m)tetrazole, O(CH₂)_(n)-biphenyl-(CH₂)_(m)CN, O(CH₂)_(n)-biphenyl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-biphenyl, NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CO₂R, NR(CH₂)_(n)-biphenyl-(CH₂)_(m)tetrazole, NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CN, NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl, O(CH₂)_(n)-heteroaryl, NR(CH₂)_(n)-aryl, NR(CH₂)_(n)-heteroaryl, O(CH₂)_(n)-aryl(CH₂)_(m)CO₂R, O(CH₂)_(n)-aryl-C₂₋₄ alkenyl-CO₂R, O(CH₂)_(n)-aryl(CH₂)_(m)-tetrazole, O(CH₂)_(n)-aryl(CH₂)_(m)CN, O(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl(CH₂)_(m)—PO(OR)₂, O(CH₂)_(n)-aryl-O(CH₂)_(n)CO₂R, O(CH₂)_(n)-aryl-O—C₂₋₄ alkenyl-CO₂R, O(CH₂)_(n)-arylO(CH₂)_(n)-tetrazole, O(CH₂)_(n)-arylO(CH₂)_(n)CN, O(CH₂)_(n)-arylO(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-arylO(CH₂)_(n)—PO(OR)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CO₂R, O(CH₂)_(n)-aryl-NRC₂₋₄ alkenyl-CO₂R, O(CH₂)_(n)-aryl-NR(CH₂)_(n)-tetrazole, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CN, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)—PO(OR)₂, NR(CH₂)_(n)-aryl(CH₂)_(m)CO₂R, NR(CH₂)_(n)-aryl-C₂₋₄ alkenyl-CO₂R, NR(CH₂)_(n)-aryl(CH₂)_(m)-tetrazole, NR(CH₂)_(n)-aryl(CH₂)_(m)CN, NR(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-aryl(CH₂)_(m)—PO(OR)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)-aryl-NR—C₂₋₄ alkenyl-CO₂R, NR(CH₂)_(n)-aryl-NR(CH₂)_(m)tetrazole, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CN, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)-arylO(CH₂)_(n)CO₂R, NR(CH₂)_(n)-aryl-O—C₂₋₄ alkenyl-CO₂R, NR(CH₂)_(n)-aryl-O(CH₂)_(n-)tetrazole, NR(CH₂)_(n)-arylO(CH₂)_(n)CN, NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-arylO(CH₂)_(n)PO(OR)₂, O(CH₂)_(n)-heteroaryl(CH₂)_(m)CO₂R, O(CH₂)_(n)-heteroaryl-C₂₋₄ alkenyl-CO₂R, O(CH₂)_(n)-heteroaryl(CH₂)_(m)-tetrazole, O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CN, O(CH₂)_(n)-heteroaryl(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-heteroaryl(CH₂)_(m)—PO(OR)₂, O(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CO₂R, O(CH₂)_(n)-heteroaryl-O—C₂₋₄ alkenyl-CO₂R, O(CH₂)_(n)-heteroarylO(CH₂)_(n)-tetrazole, O(CH₂)_(n)-heteroaryl O(CH₂)_(n)CN, O(CH₂)_(n)-heteroarylO(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroarylO(CH₂), —PO(OR)₂, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CO₂R, O(CH₂)_(n)-heteroaryl-NR—C₂₋₄ alkenyl-CO₂R, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)-tetrazole, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CN, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)—PO(OR)₂, NR(CH₂)_(n)-heteroaryl(CH₂)_(m)CO₂R, NR(CH₂)_(n)-heteroaryl-C₂₋₄ alkenyl-CO₂R, NR(CH₂)_(n)-heteroaryl(CH₂)_(m)-tetrazole, NR(CH₂)_(n)-heteroaryl(CH₂)_(m)CN, NR(CH₂)_(n)-heteroaryl(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-heteroaryl(CH₂)_(m)—PO(OR)₂, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)-heteroaryl-NR—C₂₋₄ alkenyl-CO₂R, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n-)tetrazole, NR(CH₂)_(n) heteroaryl-NR(CH₂)_(n)CN, NR(CH₂)_(n)-heteroaryl-NR(CH₂)^(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CO₂R, NR(CH₂)_(n)-heteroaryl-O—C₂₋₄ alkenyl-CO₂R, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n-)tetrazole, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CN, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroarylO(CH₂)_(n)PO(OR)₂, and O(CH₂CH₂O)_(p)CH₂CH₂OR³, where heteroaryl is a 5-12 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X² and tetrazole is substituted with 0-1 R.
 10. A compound of claim 1, wherein the compound is of formula Ic, or a stereoisomer or a pharmaceutically acceptable salt thereof:

wherein: R, at each occurrence, is independently selected from H and C₁₋₄ alkyl; R¹ is selected from H and C₁₋₄ alkyl; X and X¹ are independently selected from H, OR, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl, N(R)₂, (CH₂)_(m)CONR₂, (CH₂)_(m)CN, NRCO(CH₂)_(n)CON(R)₂, NRSO₂CH₃, SO₂NRCH₃, CH₂N(C₁₋₄ alkyl)₂, CH₂-aryl, CH₂-heteroaryl, O(CH₂)_(n)-aryl, O(CH₂)_(n)-heteroaryl, NR(CH₂)_(n)-aryl, NR(CH₂)_(n)-heteroaryl, O(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-biphenyl, O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CONH₂, NR(CH₂)_(n)-biphenyl, NR(CH₂)_(n)-biphenyl-CN, NR(CH₂)_(n)-biphenyl-CONH₂, and O(CH₂CH₂O)_(p)CH₂CH₂OR³, where heteroaryl is a 5-10 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X²; R³ is selected from H, C₁₋₄ alkyl, and aryl-C₁₋₄ alkyl-; X², at each occurrence, is independently selected from H, OR, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, —CN, C(O)NR₂, NRSO₂CH₃, and SO₂N(R)C₁₋₄alkyl; and, Z is selected from H, OH, C₁₋₄ alkoxy, O—C₂₋₄ alkenyl, O(CH₂)_(n)CONH₂, OCH₂-aryl, NRR, NR—C₂₋₄ alkenyl, NR(CH₂)_(n)CONH₂, and NRCH₂-aryl, wherein aryl is substituted with 1-2 X²; and, provided that at least one of X and X¹ is other than H, alkyl, alkoxy, hydroxy, and halo.
 11. A compound of claim 10, wherein: one of X and X¹ is H and the other selected from C₂₋₄ alkenyl, C₂₋₄ alkynyl, CF₃, nitro, O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl, N(R)₂, (CH₂)_(m)CONR₂, (CH₂)_(m)CN, NRCO(CH₂)_(n)CON(R)₂, NRSO₂CH₃, SO₂NRCH₃, CH₂N(C₁₋₄ alkyl)₂, CH₂-aryl, CH₂-heteroaryl, O(CH₂)_(n)-aryl, O(CH₂)_(n)-heteroaryl, NR(CH₂)_(n)-aryl, NR(CH₂)_(n)-heteroaryl, O(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-biphenyl, O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CONH₂, NR(CH₂)_(n)-biphenyl, NR(CH₂)_(n)-biphenyl-CN, NR(CH₂)_(n)-biphenyl-CONH₂, and O(CH₂CH₂O)_(p)CH₂CH₂OR³, where heteroaryl is a 5-10 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X².
 12. A compound of claim 1, wherein the compound is of formula IIa, or a stereoisomer or a pharmaceutically acceptable salt thereof:

wherein: R, at each occurrence, is independently selected from H and C₁₋₆ alkyl; R¹ is selected from H and C₁₋₄ alkyl; R² is selected from H and C₁₋₄ alkyl; X and X¹ are independently selected from H, OR, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl, (CH₂)_(m)CONR₂, (CH₂)_(m)CN, NRCO(CH₂)_(n)CON(R)₂, NRSO₂CH₃, SO₂NRCH₃, CH₂-aryl, CH₂-heteroaryl, O(CH₂)_(n)-aryl, O(CH₂)_(n)-heteroaryl, NR(CH₂)_(n)-aryl, NR(CH₂)_(n)-heteroaryl, O(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-aryl; O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-biphenyl, O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CONH₂, NR(CH₂)_(n)-biphenyl, NR(CH₂)_(n)-biphenyl-CN, and NR(CH₂)_(n)-biphenyl-CONH₂, and O(CH₂CH₂O)_(p)CH₂CH₂OR³, where heteroaryl is a 5-10 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X²; R³ is selected from H, C₁₋₄ alkyl, and aryl-C₁₋₄ alkyl-; X², at each occurrence, is independently selected from H, OR, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, —CN, C(O)NR₂, NRSO₂CH₃, and SO₂N(R)C₁₋₄alkyl; Y is selected from O and H₂; when Y is H₂, Z¹ is selected from H and OR; when Y is O, Z¹ is selected from NRR, NR(CH₂)_(n)CONH₂, NR—C₂₋₄ alkenyl, and NR(CH₂)_(n)-aryl, wherein aryl is substituted with 1-2 X²; Q is selected from O⁻, C₁₋₄ alkyl, C₃₋₄ alkenyl, and C₃₋₄ alkynyl; and, provided that when Q is other than O⁻, A⁻ is present and is selected from Cl and Br; further provided that at least one of X and X¹ is other than H, alkyl, alkoxy, hydroxy, and halo.
 13. A compound of claim 12, wherein: one of X and X¹ is H and the other selected from C₂₋₄ alkenyl, C₂₋₄ alkynyl, CF₃, nitro, O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl, (CH₂)_(m)CONR₂, (CH₂)_(m)CN, NRCO(CH₂)_(n)CON(R)₂, NRSO₂CH₃, SO₂NRCH₃, CH₂-aryl, CH₂-heteroaryl, O(CH₂)_(n)-aryl, O(CH₂)_(n)-heteroaryl, NR(CH₂)_(n)-aryl, NR(CH₂)_(n)-heteroaryl, O(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-aryl, O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-biphenyl, O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CONH₂, NR(CH₂)_(n)-biphenyl, NR(CH₂)_(n)-biphenyl-CN, and NR(CH₂)_(n)-biphenyl-CONH₂, and O(CH₂CH₂O)_(p)CH₂CH₂OR³, where heteroaryl is a 5-10 membered ring system consisting of carbon atoms and from 1-4 heteroatoms selected from N, O, and S, and wherein aryl, biphenyl, and heteroaryl are substituted with 1-2 X².
 14. A compound selected from Table A and B, or a stereoisomer or pharmaceutically acceptable salt thereof.
 15. A compound selected from I, IIa, IIb, IIIa, IIIb, IVa, IVb, IVc, IVd, V, VI, VII, VIIIa, VIIIb, VIIIc, VIIId, IXa, IXb, Xa, and Xb, or a stereoisomer or pharmaceutically acceptable salt thereof.
 16. A pharmaceutical composition, comprising: a compound of claim 1 and a pharmaceutically acceptable carrier.
 17. A method of treating a disease, comprising: administering to a mammal in need thereof a therapeutically effective amount of a compound of claim 1 or a stereoisomer or pharmaceutically acceptable salt thereof, wherein the disease is selected from obesity, diabetes, cardiometabolic disorders, and a combination thereof.
 18. A method of treating a disease, comprising: administering to a mammal in need thereof a therapeutically effective amount of a compound of claim 1 or a stereoisomer or pharmaceutically acceptable salt thereof, wherein the disease is a co-morbidty of obesity.
 19. A method of treating a disease, comprising: administering to a mammal in need thereof a therapeutically effective amount of a compound of claim 1 or a stereoisomer or pharmaceutically acceptable salt thereof, wherein the disease is a CNS disorder. 